Publisher: Elsevier   (Total: 3206 journals)

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Showing 1 - 200 of 3206 Journals sorted alphabetically
Academic Pediatrics     Hybrid Journal   (Followers: 39, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 27, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 106, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 28, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 44, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 8)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6)
Acta Astronautica     Hybrid Journal   (Followers: 449, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 30, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 3)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 11, SJR: 0.18, CiteScore: 1)
Acta Histochemica     Hybrid Journal   (Followers: 5, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 334, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 12, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 2, SJR: 1.793, CiteScore: 6)
Acta Psychologica     Hybrid Journal   (Followers: 26, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access   (Followers: 1)
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access   (Followers: 1)
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 7, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 8)
Acute Pain     Full-text available via subscription   (Followers: 15, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 18, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 9, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 13, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 193, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 13, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 20, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 30, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 12, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 12, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 24, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 15, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 35, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 5)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 14)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 29, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 11, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 11, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 27, SJR: 1.562, CiteScore: 3)
Advances in Clinical Radiology     Full-text available via subscription   (Followers: 1)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 21, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Cosmetic Surgery     Full-text available via subscription   (Followers: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 16)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 14)
Advances in Digestive Medicine     Open Access   (Followers: 14)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 7)
Advances in Drug Research     Full-text available via subscription   (Followers: 26)
Advances in Ecological Research     Full-text available via subscription   (Followers: 44, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 30, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 9)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 51, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 2)
Advances in Family Practice Nursing     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 69, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 17)
Advances in Genetics     Full-text available via subscription   (Followers: 21, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 8, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 26, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 26)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 4, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 37, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 10, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 10, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 21, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 17, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 9, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 5, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 26)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Pathology     Hybrid Journal   (Followers: 1)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 5)
Advances in Oncobiology     Full-text available via subscription   (Followers: 2)
Advances in Ophthalmology and Optometry     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 18, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 6, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 27, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 19)
Advances in Pharmacology     Full-text available via subscription   (Followers: 17, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 10, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 10)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 6)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 19)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 69)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 7, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (Followers: 3, SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 7)
Advances in Space Research     Full-text available via subscription   (Followers: 434, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 6)
Advances in Surgery     Full-text available via subscription   (Followers: 13, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 36, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 20)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
Advances in Virus Research     Full-text available via subscription   (Followers: 6, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 57, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 396, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 12, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 485, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 18, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 32, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 47, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 4)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 58, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 8, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 12, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 12)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 2, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 11, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 11, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 56, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 6, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 6, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 5)
American Heart J.     Hybrid Journal   (Followers: 59, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 67, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 48, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 13)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 16, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 40, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 34, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 37, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 51)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics & Gynecology MFM     Hybrid Journal   (Followers: 1)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 274, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 67, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 32, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 29, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 39, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 7)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 67, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 26, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription   (Followers: 1)
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 6, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 44, SJR: 1.512, CiteScore: 5)
Analytica Chimica Acta : X     Open Access  
Analytical Biochemistry     Hybrid Journal   (Followers: 220, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 13, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 14)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 25, SJR: 0.683, CiteScore: 2)

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Similar Journals
Journal Cover
Advances in Protein Chemistry and Structural Biology
Journal Prestige (SJR): 0.791
Citation Impact (citeScore): 2
Number of Followers: 20  
 
  Full-text available via subscription Subscription journal
ISSN (Online) 1876-1623
Published by Elsevier Homepage  [3206 journals]
  • The impact of microRNAs on alterations of gene regulatory networks in
           allergic diseases
    • Abstract: Publication date: Available online 12 February 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Indoumady Baskara-Yhuellou, Jörg TostAbstractAllergic diseases including asthma are worldwide on the rise and contribute significantly to health expenditures. Allergic diseases are prototypic diseases with a strong gene by environment interaction component and epigenetic mechanisms might mediate the effects of the environment on the disease phenotype. MicroRNAs, small non-coding RNAs (miRNAs), regulate gene expression post-transcriptionally. Functional single-stranded miRNAs are generated in multiple steps of enzymatic processing from their precursors and mature miRNAs are included into the RNA-induced silencing complex (RISC). They imperfectly base-pair with the 3′UTR region of targeted genes leading to translational repression or mRNA decay. The cellular context and microenvironment as well the isoform of the mRNA control the dynamics and complexity of the regulatory circuits induced by miRNAs that regulate cell fate decisions and function. MiR-21, miR-146a/b and miR-155 are among the best understood miRNAs of the immune system and implicated in different diseases including allergic diseases. MiRNAs are implicated in the induction of the allergy reinforcing the Th2 phenotype (miR-19a, miR-24, miR-27), while other miRNAs promote regulatory T cells associated with allergen tolerance or unresponsiveness. In the current chapter we describe in detail the biogenesis and regulatory function of miRNAs and summarize current knowledge on miRNAs in allergic diseases and allergy relevant cell fate decisions focusing mainly on immune cells. Furthermore, we evoke the principles of regulatory loops and feedback mechanisms involving miRNAs on examples with relevance for allergic diseases. Finally, we show the potential of miRNAs and exosomes containing miRNAs present in several biological fluids that can be exploited with non-invasive procedures for diagnostic and potentially therapeutic purposes.
       
  • Computational model to analyze and characterize the functional mutations
           of NOD2 protein causing inflammatory disorder – Blau syndrome
    • Abstract: Publication date: Available online 4 February 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): D. Thirumal Kumar, S. Udhaya Kumar, Ahmed Shaikh Nishaat Laeeque, Shivalkar Apurva Abhay, R. Bithia, R. Magesh, Maignana Kumar, Hatem Zayed, C. George Priya DossAbstractBlau syndrome (BS), which affects the eyes, skin, and joints, is an autosomal dominant genetic inflammatory disorder. BS is caused by mutations in the NOD2 gene. However, there are no direct treatments, and treatment with conventional anti-inflammatory drugs such as adrenal glucocorticoids, anti-metabolites, and biological agents such as anti-TNF and infliximab have all been attempted with varying degrees of success. In this study, we tried to identify all the reported mutations in the NOD2 protein that cause BS. Collectively, 114 missense mutations were extracted from the UniProt, ClinVar, and HGMD databases. The mutations were further subjected to pathogenic, stability, and conservation analyses. According to these computational analyses, six missense mutations (R334Q, R334W, E383G, E383K, R426H, and T605P) were found to be highly deleterious, destabilizing, and positioned in the conserved position. ADP to ATP conversion plays a crucial role in switching the closed-form of NOD2 protein to the open-form, thus activating the protein. Accordingly, the mutations in the ADP binding sites have received more attention in comparison to the mutations in the non-ADP binding positions. Interestingly, the W490L mutation is positioned in the ADP binding site and exhibits highly deleterious and destabilizing properties. Additionally, W490L was also found to be conserved, with a ConSurf score of 7. Therefore, we further performed homology modeling to determine the 3D structure of native NOD2 and the W490L mutant. Molecular docking analysis was carried out to understand the change in the interaction of ADP with the NOD2 protein. We observed that ADP had a stronger interaction with the native NOD2 protein compared to the W490L mutant. Finally, ADP complexed with native NOD2 and W490L mutant were subjected to molecular dynamics simulations, and the trajectories were analyzed. In the simulations, we observed decreased deviation and fluctuations in native NOD2, whereas decreased compactness and inter- and intramolecular hydrogen bonds were observed in the W490L mutant. This study is expected to serve as a platform for developing targeted drug therapy for BS.
       
  • Comprehensive in silico screening and molecular dynamics studies of
           missense mutations in Sjogren-Larsson syndrome associated with the ALDH3A2
           gene
    • Abstract: Publication date: Available online 4 February 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): S. Udhaya Kumar, D. Thirumal Kumar, Pinky D. Mandal, Srivarshini Sankar, Rishin Haldar, Balu Kamaraj, Charles Emmanuel Jebaraj Walter, R. Siva, C. George Priya Doss, Hatem ZayedAbstractSjögren–Larsson syndrome (SLS) is an autoimmune disorder inherited in an autosomal recessive pattern. To date, 80 missense mutations have been identified in association with the Aldehyde Dehydrogenase 3 Family Member A2 (ALDH3A2) gene causing SLS. Disruption of the function of ALDH3A2 leads to excessive accumulation of fat in the cells, which interferes with the normal function of protective membranes or materials that are necessary for the body to function normally. We retrieved 54 missense mutations in the ALDH3A2 from the OMIM, UniProt, dbSNP, and HGMD databases that are known to cause SLS. These mutations were examined with various in silico stability tools, which predicted that the mutations p.S308N and p.R423H that are located at the protein-protein interaction domains are the most destabilizing. Furthermore, to determine the atomistic-level differences within the protein-protein interactions owing to mutations, we performed macromolecular simulation (MMS) using GROMACS to validate the motion patterns and dynamic behavior of the biological system. We found that both mutations (p.S380N and p.R423H) had significant effects on the protein-protein interaction and disrupted the dimeric interactions. The computational pipeline provided in this study helps to elucidate the potential structural and functional differences between the ALDH3A2 native and mutant homodimeric proteins, and will pave the way for drug discovery against specific targets in the SLS patients.
       
  • Protein-protein interactions: a structural view of inhibition strategies
           and the IL-23/IL-17 axis
    • Abstract: Publication date: Available online 24 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Samantha J. Allen, Kevin J. LumbAbstractProtein-protein interactions are central to biology and provide opportunities to modulate disease with small-molecule or protein therapeutics. Recent developments in the understanding of the tractability of protein-protein interactions are discussed with a focus on the ligandable nature of protein-protein interaction surfaces. General principles of inhibiting protein-protein interactions are illustrated with structural biology examples from six members of the IL-23/IL-17 signaling family (IL-1, IL-6, IL-17, IL-23 RORγT and TNFα). These examples illustrate the different approaches to discover protein-protein interaction inhibitors on a target-specific basis that has proven fruitful in terms of discovering both small molecule and biologic based protein-protein interaction inhibitors.
       
  • Expression of placental glucose transporter proteins in pregnancies
           complicated by fetal growth disorders
    • Abstract: Publication date: Available online 22 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Paweł Jan Stanirowski, Michał Lipa, Dorota Bomba-Opoń, Mirosław WielgośAbstractDuring pregnancy fetal growth disorders, including fetal macrosomia and fetal growth restriction (FGR) are associated with numerous maternal-fetal complications, as well as due to the adverse effect of the intrauterine environment lead to an increased morbidity in adult life. Accumulating evidence suggests that occurrence of fetal macrosomia or FGR, may be associated with alterations in the transfer of nutrients across the placenta, in particular of glucose. The placental expression and activity of specific GLUT transporters are the main regulatory factors in the process of maternal-fetal glucose exchange. This review article summarizes the results of previous studies on the expression of GLUT transporters in the placenta, concentrating on human pregnancies complicated by intrauterine fetal growth disorders. Characteristics of each transporter protein found in the placenta is presented, alterations in the location and expression of GLUT isoforms observed in individual placental compartments are described, and the factors regulating the expression of selected GLUT proteins are examined. Based on the above data, the potential function of each GLUT isoform in the maternal-fetal glucose transfer is determined. Further on, a detailed analysis of changes in the expression of glucose transporters in pregnancies complicated by fetal growth disorders is given, and significance of these modifications for the pathogenesis of fetal macrosomia and FGR is discussed. In the final part novel interventional approaches that might reduce the risk associated with abnormalities of intrauterine fetal growth through modifications of placental GLUT-mediated glucose transfer are explored.
       
  • Advances in Protein Chemistry and Structural Biology
    • Abstract: Publication date: 2020Source: Advances in Protein Chemistry and Structural Biology, Volume 119Author(s):
       
  • Tracking the functional meaning of the human oral-microbiome
           protein-protein interactions
    • Abstract: Publication date: Available online 16 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Nuno Rosa, Bruno Campos, Ana Cristina Esteves, Ana Sofia Duarte, Maria José Correia, Raquel M. Silva, Marlene BarrosAbstractThe interactome – the network of protein-protein interactions (PPIs) within a cell or organism – is technically difficult to assess. Bioinformatic tools can, not only, identify potential PPIs that can be later experimentally validated, but also be used to assign functional meaning to PPIs.Saliva's potential as a non-invasive diagnostic fluid is currently being explored by several research groups. But, in order to fully attain its potential, it is necessary to achieve the full characterization of the mechanisms that take place within this ecosystem.The onset of omics technologies, and specifically of proteomics, delivered a huge set of data that is largely underexplored. Quantitative information relative to proteins within a given context (for example a given disease) can be used by computational algorithms to generate information regarding PPIs. These PPIs can be further analyzed concerning their functional meaning and used to identify potential biomarkers, therapeutic targets, defense and pathogenicity mechanisms.We describe a computational pipeline that can be used to identify and analyze PPIs between human and microbial proteins. The pipeline was tested within the scenario of human PPIs of systemic (Zika Virus infection) and of oral conditions (Periodontal disease) and also in the context of microbial interactions (Candida-Streptococcus) and showed to successfully predict functionally relevant PPIs.The pipeline can be applied to different scientific areas, such as pharmacological research, since a functional meaningful PPI network can provide insights on potential drug targets, and even new uses for existing drugs on the market.
       
  • Computational approaches for identifying potential inhibitors on targeting
           protein interactions in drug discovery
    • Abstract: Publication date: Available online 13 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Vishnupriya Kanakaveti, Anusuya Shanmugam, C. Ramakrishnan, P. Anoosha, R. Sakthivel, S.K. Rayala, M. Michael GromihaAbstractIn the era of big data, the interplay of artificial and human intelligence is the demanding job to address the concerns involving exchange of decisions between both sides. Drug discovery is one of the key sources of the big data, which involves synergy among various computational methods to achieve a clinical success. Rightful acquisition, mining and analysis of the data related to ligand and targets are crucial to accomplish reliable outcomes in the entire process. Novel designing and screening tactics are necessary to substantiate a potent and efficient lead compounds. Such methods are emphasized and portrayed in the current review targeting protein-ligand and protein-protein interactions involved in various diseases with potential applications.
       
  • α  therapy&rft.title=Advances+in+Protein+Chemistry+and+Structural+Biology&rft.issn=1876-1623&rft.date=&rft.volume=">Inflammatory bowel disease and targeted oral anti-TNF α  therapy
    • Abstract: Publication date: Available online 10 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Owen R. Griffiths, John Landon, Ruth E. Coxon, Keith Morris, Philip James, Rachel AdamsAbstractAntibodies have provided invaluable treatment options for many diseases, with immunotherapy revolutionising the treatment of several inflammatory disorders including inflammatory bowel disease (IBD). Accumulating evidence suggests that IBD results from an inappropriate response to intestinal microbes and environmental factors in genetically susceptible individuals, with overactivity of the pro-inflammatory pathways. On a pathophysiological level, IBD is a complex disease with intestinal fibrosis, stenosis and an increased incidence of cancer observed in those whose disease is inadequately controlled over time.Regulating the actions of the pro-inflammatory cytokine human tumor necrosis factor-alpha (hTNFα) through the use of anti-TNFα monoclonal antibodies (e.g. infliximab, certolizumab, adalimumab and golimumab) has proven an effective intervention for IBD with their increased use a testament of their effectiveness. These agents are administered systemically thereby causing their distribution throughout the body in a condition that is localised to the gastrointestinal (GI) tract. Immunogenicity, the induction of anti-drug antibodies (ADAs), serum sickness and other undesirable side effects limit their use, whilst up to 50% of patients do not respond to initial therapy.Diseases confined to the GI tract are ideal for targeting by oral therapy which mitigates side effects and allows for lower doses to be administered. Several oral anti-TNFα agents have been investigated with success but are not yet in general clinical use. This partially reflects the fact that the oral administration of antibodies has many barriers including the harsh environment of the GI tract and the presence of enzymes including pepsin, trypsin and chymotrypsin in the intestine which provide significant challenges to targeted oral therapy.
       
  • Roles of Porphyromonas gingivalis and its virulence factors in
           periodontitis
    • Abstract: Publication date: Available online 10 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Weizhe Xu, Wei Zhou, Huizhi Wang, Shuang LiangAbstractPeriodontitis is an infection-driven inflammatory disease, which is characterized by gingival inflammation and bone loss. Periodontitis is associated with various systemic diseases, including cardiovascular, respiratory, musculoskeletal, and reproductive system related abnormalities. Recent theory attributes the pathogenesis of periodontitis to oral microbial dysbiosis, in which Porphyromonas gingivalis acts as a critical agent by disrupting host immune homeostasis. Lipopolysaccharide, proteases, fimbriae, and some other virulence factors are among the strategies exploited by P. gingivalis to promote the bacterial colonization and facilitate the outgrowth of the surrounding microbial community. Virulence factors promote the coaggregation of P. gingivalis with other bacteria and the formation of dental biofilm. These virulence factors also modulate a variety of host immune components and subvert the immune response to evade bacterial clearance or induce an inflammatory environment. In this chapter, our focus is to discuss the virulence factors of periodontal pathogens, especially P. gingivalis, and their roles in regulating immune responses during periodontitis progression.
       
  • Autophagy proteins and its homeostasis in cellular environment
    • Abstract: Publication date: Available online 10 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Vrushali Guhe, Bhavnita Soni, Prajakta Ingale, Shailza SinghAbstractAutophagy is a self-destructing mechanism of cell via lysosomal degradation, which helps to degrade/destroy hazardous substances, proteins, degenerating organelles and recycling nutrients. It plays an important role is cellular homeostasis and regulates internal environment of cell, moreover, when needed causes non-apoptotic programmed death of cell. Autophagy has been observed as one of the major factors in parasite clearance in leishmaniasis. Being an intra-cellular pathogen, the cell mediated response is the only alternative for adaptive immunity against Leishmania in host. Pro-inflammatory cytokines IL12 and TNFα generate Th2 response which helps in active phagocytosis of parasite whereas an anti-inflammatory cytokine like IL10 mediate parasite promotion by blocking autophagic pathways and inhibiting phagocytic actions. In the present chapter, through systems biology approach, we are trying to decipher the role of pro-inflammatory and anti-inflammatory cytokine in autophagy during leishmanial infection. TLR2/6 mediated signaling stimulated by LPG produces many pro-inflammatory cytokines like IL12, TNFα and IL6 etc. Among them TNFα, causes the activation of PI3P through a series of events, which results in activation of autophagic machinery, whereas, IL10 through ATG9 and mTOR activation, inhibits autophagy. The mathematical modeling of these pathways shows that, ATG9-PI3P act as a negative feedback loop in autophagic machinery of leishmaniasis.
       
  • Role of protein-protein interactions in allosteric drug design for DNA
           methyltransferases
    • Abstract: Publication date: Available online 10 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Zhongjie Liang, Yu Zhu, Xingyi Liu, Guang HuAbstractDNA methyltransferases (DNMTs) not only play key roles in epigenetic gene regulation, but also serve as emerging targets for several diseases, especially for cancers. Due to the multi-domains of DNMT structures, targeting allosteric sites of protein-protein interactions (PPIs) is becoming an attractive strategy in epigenetic drug discovery. This chapter aims to review the major contemporary approaches utilized for the drug discovery based on PPIs in different dimensions, from the enumeration of allosteric mechanism to the identification of allosteric pockets. These include the construction of protein structure networks (PSNs) based on molecular dynamics (MD) simulations, performing elastic network models (ENMs) and perturbation response scanning (PRS) calculation, the sequence-based conservation and coupling analysis, and the allosteric pockets identification. Furthermore, we complement this methodology by highlighting the role of computational approaches in promising practical applications for the computer-aided drug design, with special focus on two DNMTs, namely, DNMT1 and DNMT3A.
       
  • Structural sequence evolution and computational modeling approaches of the
           complement system in leishmaniasis
    • Abstract: Publication date: Available online 10 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Prajakta Ingale, Ritika Kabra, Shailza SinghAbstractThe complement system is one of the first barriers and consists of well-balanced cascades of reactions which generates anaphylatoxins such as C5a and C3a. A G-protein coupled receptor C5a anaphylatoxin chemotactic receptor 1 (C5AR1, also known as CD88) is the receptor for C5a which is present on cells of myeloid origin. Owing to difficulty in obtaining crystal structures of GPCRs in either inactive or active state, accurate structural modeling is still highly desirable for the majority of GPCRs. In an attempt to dissect the conformational changes associated with GPCR activation, computational modeling approaches is being pursued in this paper along with the evolutionary divergence to deal with the structural variability.
       
  • Advances in Protein Chemistry and Structural Biology
    • Abstract: Publication date: 2019Source: Advances in Protein Chemistry and Structural Biology, Volume 118Author(s):
       
  • Sphingolipids as mediators of inflammation and novel therapeutic target in
           inflammatory bowel disease
    • Abstract: Publication date: Available online 8 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Olga A. Sukocheva, Elena Lukina, Eileen McGowan, Anupam BishayeeAbstractMorbidity of inflammatory gastrointestinal (GI) diseases continues to grow resulting in worsen quality of life and increased burden on public medical systems. Complex and heterogenous illnesses, inflammatory bowel diseases (IBDs) encompass several inflammation -associated pathologies including Crohn's disease and ulcerative colitis. IBD is often initiated by a complex interplay between host genetic and environmental factors, lifestyle and diet, and intestinal bacterial components. IBD inflammatory signature was linked to the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) signaling pathway that is currently targeted by IBD therapies. Sphingolipid signaling was identified as one of the key mediators and regulators of pro-inflammatory conditions, and, specifically, TNF-α related signaling. All GI tissues and circulating immune/blood cells contain activated sphingolipid-metabolizing enzymes, including sphingosine kinases (SphK1 and SphK2) that generate sphingosine-1-phosphate (S1P), a bioactive lipid and ligand for five G-protein coupled membrane S1P receptors (S1PRs). Numerous normal and pathogenic inflammatory responses are mediated by SphK/S1P/S1PRs signaling axis including lymphocyte trafficking and activation of cytokine signaling machinery. SphK1/S1P/S1PRs axis has recently been defined as a target for the treatment of GI diseases including IBD/colitis. Several SphK1 inhibitors and S1PRs antagonists have been developed as novel anti-inflammatory agents. In this review, we discuss the mechanisms of SphK/S1P signaling in inflammation-linked GI disorders. The potential role of SphK/S1PRs inhibitors in the prevention and treatment of IBD/colitis is critically evaluated.
       
  • Targeting FOXP3 complex ensemble in drug discovery
    • Abstract: Publication date: Available online 7 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Jingyao Huang, Shuoyang Wang, Yuxin Jia, Yujia Zhang, Xueyu Dai, Bin LiAbstractForkhead Box P3 (FOXP3) is a key transcriptional regulator of regulatory T cells (Tregs), especially for its function of immune suppression. The special immune suppression function of Tregs plays an important role in maintaining immune homeostasis, and is related to several diseases including cancer, and autoimmune diseases. At the same time, FOXP3 takes a place in a large transcriptional complex, whose stability and functions can be controlled by various post-translational modification. More and more researches have suggested that targeting FOXP3 or its partners might be a feasible solution to immunotherapy. In this review, we focus on the transcription factor FOXP3 in Tregs, Treg functions in diseases and the FOXP3 targets.
       
  • Disease modifying drugs for rheumatological diseases: a brief history of
           everything
    • Abstract: Publication date: Available online 7 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Joanna L. Giles, Oktawia J. Polak, John LandonAbstractThe rheumatological diseases are a group of chronic, painful, degenerative and debilitating conditions with an increasing prevalence across the globe. The pathogenesis of these disorders is complex, overlapping and not fully understood. As such, it is difficult and time consuming to achieve correct diagnosis and complete remission for an individual patient.In this review we describe the most common forms of inflammatory arthritis and discuss how the management and treatment options for these rheumatic diseases have developed over time. We outline the successes and the limitations of current treatment regimens and discuss the economic burden of the current options.With advancements in understanding of disease mechanisms, we discuss the importance of the biologics revolution in the context of rheumatological disease and how the development of biosimilars and small molecule inhibitors will impact current treatment options in order to alleviate some of the cost burden of biological therapies.The ideal treatment strategy for the future would involve personalized and predictive medicine where by treatments can be tailored to an individual patient's needs in order to achieve fast and successful remission with no adverse events.
       
  • Combining molecular dynamics simulations and experimental analyses in
           protein misfolding
    • Abstract: Publication date: Available online 6 January 2020Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Holger Wille, Lyudmyla Dorosh, Sara Amidian, Gerold Schmitt-Ulms, Maria StepanovaAbstractThe fold of a protein determines its function and its misfolding can result in loss-of-function defects. In addition, for certain proteins their misfolding can lead to gain-of-function toxicities resulting in protein misfolding diseases such as Alzheimer's, Parkinson's, or the prion diseases. In all of these diseases one or more proteins misfold and aggregate into disease-specific assemblies, often in the form of fibrillar amyloid deposits. Most, if not all, protein misfolding diseases share a fundamental molecular mechanism that governs the misfolding and subsequent aggregation. A wide variety of experimental methods have contributed to our knowledge about misfolded protein aggregates, some of which are briefly described in this review. The misfolding mechanism itself is difficult to investigate, as the necessary timescale and resolution of the misfolding events often lie outside of the observable parameter space. Molecular dynamics simulations fill this gap by virtue of their intrinsic, molecular perspective and the step-by-step iterative process that forms the basis of the simulations. This review focuses on molecular dynamics simulations and how they combine with experimental analyses to provide detailed insights into protein misfolding and the ensuing diseases.
       
  • Protein-protein complexes as targets for drug discovery against infectious
           diseases
    • Abstract: Publication date: Available online 18 December 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Yusuf Akhter, Razak HussainAbstractAntibiotics are therapeutic agents against bacterial infections, however, the emergence of multiple and extremely drug-resistant microbes (Multi-Drug Resistant and Extremely Drug-Resistant) are compromising the effectiveness of the currently available treatment options. The drug resistance is not a novel crisis, the current pace of drug discovery has failed to compete with the growth of MDR and XDR pathogenic strains and therefore, it is highly central to find out novel antimicrobial drugs with unique mechanisms of action which may reduce the burden of MDR and XDR pathogenic strains. Protein-protein interactions (PPIs) are involved in a countless of the physiological and cellular phenomena and have become an attractive target to treat the diseases. Therefore, targeting PPIs in infectious agents may offer a completely novel strategy of intervention to develop anti-infective drugs that may combat the ever-increasing rate of drug resistant strains. This chapter describes how small molecule candidate inhibitors that are capable of disrupting the PPIs in pathogenic microbes and it could be an alternative lead discovery strategy to obtain novel antibiotics. Over the last three decades, there has been increasing efforts focused on the manipulation of PPIs in order to develop novel therapeutic interventions. The diversity and complexity of such a complex and highly dynamic systems pose many challenges in targeting PPIs by drug-like molecules with necessary selectivity and potency. Traditional and novel drug discovery strategies have provided tools for designing and assessing PPI inhibitors against infectious diseases.
       
  • Targeting arrestin interactions with its partners for therapeutic purposes
    • Abstract: Publication date: Available online 18 December 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Vsevolod V. Gurevich, Eugenia V. GurevichAbstractMost vertebrates express four arrestin subtypes: two visual ones in photoreceptor cells and two non-visuals expressed ubiquitously. The latter two interact with hundreds of G protein-coupled receptors, certain receptors of other types, and numerous non-receptor partners. Arrestins have no enzymatic activity and work by interacting with other proteins, often assembling multi-protein signaling complexes. Arrestin binding to every partner affects cell signaling, including pathways regulating cell survival, proliferation, and death. Thus, targeting individual arrestin interactions has therapeutic potential. This requires precise identification of protein-protein interaction sites of both participants and the choice of the side of each interaction which would be most advantageous to target. The interfaces involved in each interaction can be disrupted by small molecule therapeutics, as well as by carefully selected peptides of the other partner that do not participate in the interactions that should not be targeted.
       
  • Cyclin-dependent kinase inhibition: an opportunity to target
           protein-protein interactions
    • Abstract: Publication date: Available online 18 December 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Mark A. KleinAbstractCyclin-dependent kinases (CDKs) play an integral part in cellular activities. To date, most of the activities have been evaluated in the cell cycle and transcription. Several diseases are affected by abnormalities in CDKs, related-pathways, or proteins that regulate CDK activity. CDKs are primarily dependent on activation by binding other proteins, namely Cyclins. In addition, phosphorylation of key CDK residues also plays a major part in CDK activity. To date, the most successful drugs have been developed against CDK4 and CDK6 and are FDA approved for use in advanced breast cancer. However, this is likely only a small fraction of the potential for targeting CDKs as a strategy against cancer and other diseases. Based on the extensive protein-protein interactions made by CDKs with other proteins (Cyclins and others), there are numerous possibilities for targeting strategies against protein-protein interactions. Here we describe the predominant roles of CDKs in the cell, key interacting proteins, significant 3-dimensional structural characteristics, and summarize the work-to-date in inhibition of CDKs.
       
  • Latest trends in structure based drug design with protein targets
    • Abstract: Publication date: Available online 18 December 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Angshuman BagchiAbstractStructure based drug designing is an important endeavor in the field of structural bioinformatics. Previously the entire process was dependent on the wet-lab experiments to build libraries of ligand molecules. And the molecules used to be tested to determine their binding efficacies with protein target. However, the entire process is very lengthy and above all highly expensive. With the advent of supercomputers and increasing computational powers, the search process for finding suitable ligand molecules against target proteins have become more streamlined and cost-effective. Now the entire ligand search process is performed in-silico with the help of the techniques of virtual screening, molecular docking simulations and molecular dynamics studies. In the present chapter, a brief overview of the computational techniques involved in structure based drug designing is presented with a special emphasis on the thermodynamic principles behind the molecular interactions.
       
  • Atherosclerosis: orchestrating cells and biomolecules involved in its
           activation and inhibition
    • Abstract: Publication date: Available online 18 December 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Ashok Munjal, Rekha KhandiaAbstractThe term atherosclerosis refers to the condition of deposition of lipids and other substances in and on the artery walls, called as plaque that restricts the normal blood flow. The plaque may be stable or unstable in nature. Unstable plaque can burst and trigger clot formation adding further adversities. The process of plaque formation involves various stages including fatty streak, intermediate or fibro-fatty lesion and advanced lesion. The cells participating in the formation of atherosclerotic plaque include endothelial cells, vascular smooth muscle cells (VSMC), monocytes, monocytes derived macrophages, macrophages and dendritic cells and regulatory T cells (TREG). The role of a variety of cytokines and chemokines have been studied which either help in progression of atherosclerotic plaque or vice versa. The cytokines involved in atherosclerotic plaque formation include IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, IL-18, IL-20, IL-25, IL-27, IL-33, IL-37, TNF-α, TGF-β and IFN-γ; whereas amongst the chemokines (family of small cytokines) are CCL2, CCL3, CXCL4, CCL5, CXCL1, CX3CL1, CCL17, CXCL8, CXCL10, CCL20, CCL19 and CCL21 and macrophage migration-inhibitory factor. These are involved in the atherosclerosis advancements, whereas the chemokine CXCL12 is play atheroprotective roles. Apart this, contradictory functions have been documented for few other chemokines such as CXCL16. Since the cytokines and chemokines are amongst the key molecules involved in orchestrating the atherosclerosis advancements, targeting them might be an effective strategy to encumber the atherosclerotic progression. Blockage of cytokines and chemokines via the means of broad-spectrum inhibitors, neutralizing antibodies, usage of decoy receptors or RNA interference have been proved to be useful intervention against atherosclerosis.
       
  • Dietary plant flavonoids in prevention of obesity and diabetes
    • Abstract: Publication date: Available online 12 December 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Biswanath Dinda, Manikarna Dinda, Arup Roy, Subhajit DindaAbstractObesity and diabetes are the most prevailing chronic metabolic diseases worldwide from mainly lipid and glucose metabolic dysfunctions and their incidence is increasing at an alarming high rate. Obesity is characterized by excess fat accumulation in WAT and liver and is the central player of insulin resistance in the peripheral tissues from chronic inflammation, lipotoxicity and gut dysbiosis, and plays a key role for development of type 2 diabetes (T2DM) and vascular diseases. Diabetes mellitus, known as diabetes, is chiefly characterized by hyperglycaemia from impaired insulin secretion and insulin resistance. Several identified mutant genes in insulin secretion and resistance and various environmental factors are considered responsible for the onset of this disease. Currently available oral synthetic drugs, biguanides, incretin mimetic, GLP-1R and PPAR agonists and DPP-4 inhibitors for management of obesity and diabetes have several adverse effects in patients on long-term use. Emerging evidence supports the efficacy of dietary plant flavonoids in prevention and attenuation of obesity and diabetes by the protection and proliferation of pancreatic beta-cells and improvement of their insulin secretory function via activation of cAMP/PKA signaling pathway as well as in the improvement of insulin sensitivity in the peripheral metabolic tisssues for glucose uptake and utilization via inhibition of inflammation, lipotoxicity and oxidative stress. These flavonoids improve GLUT-4 expression and translocation to plasma membrane by activation of insulin-sensitive PI3K/Akt signaling and insulin-independent AMPK, SIRT-1 and MOR activation pathways for regulation of glucose homeostasis, and improve fat oxidation and reduce lipid synthesis by regulation of related genes for lipid homeostasis in the body of obese diabetic animals. In this chapter, we have highlighted all these beneficial anti-obesity and antidiabetic potentials of some dietary plant flavonoids along with their molecular actions, bioavailability and pharmacokinetics. In addition, the present understanding and management of obesity and diabetes are also focused.
       
  • The expanding pathways of autoinflammation: a lesson from the first 100
           genes related to autoinflammatory manifestations
    • Abstract: Publication date: Available online 12 December 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Riccardo Papa, Paolo Picco, Marco GattornoAbstractAutoInflammatory Diseases (AIDs) are a group of innate immune system disorders characterized by sterile inflammation without evidence of pathogenic autoantibodies or auto-reactive T lymphocytes. An expanding spectrum of genes and molecular pathways are associated with AIDs.Inflammasomopathies are secondary to dysregulation of multi-protein complexes, called inflammasomes, leading to an excessive maturation and secretion of IL1β and IL18. Patients present with persistent or recurrent systemic inflammation, abdominal and chest pain, skin rashes and are sensible to IL1 inhibitors.Unfolded proteins response causes a small number of AIDs that we propose to call immuno-proteinopathies, characterized by recurrent fevers and deep tissues inflammation.Other inflammatory conditions can occur in case of abnormalities of actin polymerization and the term of immuno-actinopathies is proposed.Generalized pustular psoriasis is a marker of autoinflammation mainly affecting the keratinocytes. Specific treatment targeting the p40 subunit of IL12 and IL23 or IL-17 are usually effective.Granulomatous inflammation characterizes AIDs related to NOD2 signaling defects.Defects in the ubiquitin-proteasome system cause a group of relopathies and some interferonopathies related to defect of the proteasome function (CANDLE syndrome).Gain of function of proteins regulating the production of type I interferons lead to severe inflammatory conditions, called interferonopathies. The JAK/STAT inhibitors are usually effective in these latter conditions.In conclusions, the identification of the main intracellular pathways involved in rare monogenic AIDs allows not only the proper classification of different conditions, but also highlight a pivotal role of possible novel therapeutic targets for the future.
       
  • Mass spectrometric approaches for profiling protein folding and stability
    • Abstract: Publication date: Available online 26 November 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Joseph C. GenereuxAbstractProtein stability reports on protein homeostasis, function, and binding interactions, such as to other proteins, metabolites and drugs. As such, there is a pressing need for technologies that can report on protein stability. The ideal technique could be applied in vitro or in vivo systems, proteome-wide, independently of matrix, under native conditions, with residue-level resolution, and on protein at endogenous levels. Mass spectrometry has rapidly become a preferred technology for identifying and quantifying proteins. As such, it has been increasingly incorporated into methodologies for interrogating protein stability and folding. Although no single technology can satisfy all desired applications, several emerging approaches have shown outstanding success at providing biological insight into the stability of the proteome. This chapter outlines some of these recent emerging technologies.
       
  • Pattern recognition receptors as potential drug targets in inflammatory
           disorders
    • Abstract: Publication date: Available online 26 November 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Declan P. McKernanAbstractPattern recognition receptors (PRRs) are a key part of the innate immune system, the body's first line of defense against infection and tissue damage. This superfamily of receptors including Toll-like receptors (TLRs), NOD-like receptors (NLRs), C-type lectin-like receptors (CLRs) and RIG-like receptors (RLRs) are responsible for initiation of the inflammatory response by their recognition of molecular patterns present in invading microorganisms (such as bacteria, viruses or fungi) during infection or in molecules released following tissue damage during acute or chronic disease states (such as sepsis or arthritis). These receptors are widely expressed and located on the cell surface, in intracellular compartments or in the cytoplasm can detect a single or subset of molecules including lipoproteins, carbohydrates or nucleic acids. In response, they initiate an intracellular signaling cascade that culminates in the synthesis and release of cytokines, chemokines and vasoactive molecules. These steps are necessary to maintain tissue homeostasis and remove potentially dangerous pathogens. However, during extreme or acute responses or during chronic disease, this can be damaging and even lead to death. Therefore, it is thought that targeting such receptors may offer a therapeutic approach in chronic inflammatory diseases or in cases of acute infection leading to sepsis. Herein, the current knowledge on the molecular biology of PRRs is reviewed along with their association with inflammatory and infectious diseases. Finally, the testing of therapeutic compounds and their future merit as targets is discussed.
       
  • Functional and dysfunctional folding, association and aggregation of
           caseins
    • Abstract: Publication date: Available online 26 November 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): John A. Carver, Carl HoltAbstractCaseins are a group of closely related intrinsically disordered proteins (IDPs), best known for their occurrence in milk as stable, polydisperse, roughly spherical, amorphous particles, typically containing thousands of protein chains and hundreds of nanoclusters of calcium phosphate. The particles are called casein micelles though their structure bears no resemblance to detergent micelles. Caseins have an open and flexible conformation with a preponderance of poly-l-proline II secondary structure and hence cannot be described as hydrophobic proteins. Individually, and in combination, they associate through polar and non-polar interactions to form polydisperse fuzzy complexes (including the native casein micelle) while retaining their hydrated and flexible conformation to a large degree. Like many other IDPs, caseins are prone to form cytotoxic amyloid fibrils. However, they are also highly effective molecular chaperones so that a mixture of different caseins can form fuzzy complexes that are often self-limiting in size and, within which, amyloid fibril formation is suppressed. The remarkable ability of caseins to sequester nanoclusters of calcium phosphate in stable complexes is due to their flexible conformation and multiply-phosphorylated short sequences. These features combine to form a dense peptide shell around the calcium phosphate making the core-shell complex thermodynamically stable, even at high calcium and phosphate concentrations. Thus, the casein micelle provides a readily digested, high calcium food for the neonate. It also preserves the functional properties of caseins as IDPs and protects the mammary gland against amyloid formation and pathological calcification, dysfunctional processes that would reduce the future reproductive success of the mother.
       
  • The intrinsic and extrinsic factors that contribute to proteostasis
           decline and pathological protein misfolding
    • Abstract: Publication date: Available online 26 November 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Elise A. KikisAbstractProteostasis refers to the ability of cells to maintain the health of the proteome. Highly conserved quality control mechanisms exist to maintain proteostasis. These include the heat shock response, the unfolded protein response, and protein clearance/degradation pathways. Together, these mechanisms and others comprise the proteostasis network. This network is under constant assault and is strikingly sensitive to changes in the protein folding environment, resulting in proteostasis collapse under certain conditions. Here, the intrinsic and extrinsic stresses experienced by the proteostasis network are explored. The intrinsic stresses include genetic background as well as transcriptional and translational fidelity. These cause changes in the abundance or amino acid sequence of cellular proteins. Extrinsic stresses refer to environmental perturbation of the proteome, such as those caused by temperature stress, oxidative stress, air pollution and cigarette smoke. As the stress to the proteome exceeds the capacity of the proteostasis network, progressive neurodegenerative diseases of aging, such as Alzheimer's disease and Huntington's disease are more likely to ensue.
       
  • Theoretical and computational advances in protein misfolding
    • Abstract: Publication date: Available online 26 November 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Parbati BiswasAbstractMisfolded proteins escape the cellular quality control mechanism and fail to fold properly or remain correctly folded leading to a loss in their functional specificity. Thus misfolding of proteins cause a large number of very different diseases ranging from errors in metabolism to various types of complex neurodegenerative diseases. A theoretical and computational perspective of protein misfolding is presented with a special emphasis on its salient features, mechanism and consequences. These insights quantitatively analyze different determinants of misfolding, that may be applied to design disease specific molecular targets.
       
  • Glycosylation changes in inflammatory diseases
    • Abstract: Publication date: Available online 26 November 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Sophie Groux-Degroote, Sumeyye Cavdarli, Kenji Uchimura, Fabrice Allain, Philippe DelannoyAbstractGlycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of biological functions including cell-cell and cell-substrate interactions, bacterial adhesion, cell immunogenicity and cell signaling. Alterations of glycosylation are observed in a number of inflammatory diseases. Pro-inflammatory cytokines have been shown to modulate cell surface glycosylation by regulating the expression of glycosyltransferases and sulfotransferases involved in the biosynthesis of glycan chains, inducing the expression of specific carbohydrate antigens at the cell surface that can be recognized by different types of lectins or by bacterial adhesins, contributing to the development of diseases. Glycosylation can also regulate biological functions of immune cells by recruiting leukocytes to inflammation sites with pro- or anti-inflammatory effects. Cell surface proteoglycans provide a large panel of binding sites for many mediators of inflammation, and regulate their bio-availability and functions. In this review, we summarize the current knowledge of the glycosylation changes occurring in mucin type O-linked glycans, glycosaminoglycans, as well as in glycosphingolipids, with a particular focus on cystic fibrosis and neurodegenerative diseases, and their consequences on cell interactions and disease progression.
       
  • Microglial NLRP3 inflammasome activation in multiple sclerosis
    • Abstract: Publication date: Available online 26 November 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Melis Olcum, Bora Tastan, Cagla Kiser, Sermin Genc, Kursad GencAbstractMultiple sclerosis (MS) is a chronic, autoimmune and neuroinflammatory disease of the central nervous system (CNS) mediated by autoreactive T cells directed against myelin antigens. Although the crucial role of adaptive immunity is well established in MS, the contribution of innate immunity has only recently been appreciated. Microglia are the main innate immune cells of the CNS. Similar to other myeloid cells, microglia recognize both exogenous and host-derived endogenous danger signals through pattern recognition receptors (PRRs) localized on their cell surface such as Toll Like receptor 4, or in the cytosol such as NLRP3. The second one is the sensor protein of the multi-molecular NLRP3 inflammasome complex in activated microglia that promotes the maturation and secretion of proinflammatory cytokines, interleukin-1β and interleukin-18. Overactivation of microglia and aberrant activation of the NLRP3 inflammasome have been implicated in the pathogenesis of MS. Indeed, experimental data, together with post-mortem and clinical studies have revealed an increased expression of NLRP3 inflammasome complex elements in microglia and other immune cells. In this review, we focus on microglial NLRP3 inflammasome activation in MS. First, we overview the basic knowledge about MS, microglia and the NLRP3 inflammasome. Then, we summarize studies about microglial NLRP3 inflammasome activation in MS and its animal models. We also highlight experimental therapeutic approaches that target different steps of NLRP inflammasome activation. Finally, we discuss future research avenues and new methods in this rapidly evolving area.
       
  • Using evasins to target the chemokine network in inflammation
    • Abstract: Publication date: Available online 26 November 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Shoumo Bhattacharya, Akane KawamuraAbstractInflammation, is driven by a network comprising cytokines, chemokines, their target receptors and leukocytes, and is a major pathologic mechanism that adversely affects organ function in diverse human diseases. Despite being supported by substantial target validation, no successful anti-chemokine therapeutic to treat inflammatory disease has yet been developed. This is in part because of the robustness of the chemokine network, which emerges from a large total chemokine load in disease, promiscuous expression of receptors on leukocytes, promiscuous and synergistic interactions between chemokines and receptors, and feedforward loops created by secretion of chemokines by leukocytes themselves. Many parasites, including viruses, helminths and ticks, evade the chemokine network by producing proteins that bind promiscuously to chemokines or their receptors. Evasins - three small glycoproteins identified in the saliva of the brown dog tick - bind multiple chemokines, and are active in several animal models of inflammatory disease. Over 50 evasin homologs have recently been identified from diverse tick species. Characterization of the chemokine binding patterns of evasins show that several have anti-chemokine activities that extend substantially beyond those previously described. These studies indicate that evasins function at the site of the tick bite by reducing total chemokine load. This not only reduces chemokine signaling to receptors, but also interrupts feedforward loops, thus disabling the chemokine network. Taking the lead from nature, a goal for the development of new anti-chemokine therapeutics would be to reduce the total chemokine load in disease. This could be achieved by administering appropriate evasin combinations or by smaller peptides that mimic evasin action.
       
  • Interplay between inflammation and cancer
    • Abstract: Publication date: Available online 26 November 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Rekha Khandia, Ashok MunjalAbstractDuring the 19th century, for the first time, the linkage between inflammation and cancer was established. Inflammatory microenvironment is an essential component of the tumor microenvironment. Chronic inflammation due to persistent infection due to the microbes, viruses, helminths or constant exposure to non-infectious factors like smoke, silica or asbestos eventually might result in carcinogenesis. In tumor microenvironment, various inflammatory cells such as T lymphocytes (occasionally B cells), dendritic cells, macrophages, monocytes, neutrophils and natural killer (NK) cells are present. As a mediator of immune surveillance and host defense TRAIL cytokines are produced which upon binding with death receptors (DRs) initiate a cascade of apoptotic pathways. Anti-inflammatory drugs such as aspirin, celecoxib, diclofenac, diflunisal and ibuprofen etc. are being used against cancer, indicating the interplay between both the mechanisms. A deeper understanding of common pathways implicated between both the inflammation and cancer may pave the way to fight against both of these deleterious ailments.
       
  • Misfolding of vasopressin receptors: biased agonist pharmacochaperones as
           potential therapeutics
    • Abstract: Publication date: Available online 26 November 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): C. Mendre, B. MouillacAbstractBiased agonists and pharmacological chaperones have demonstrated their potential to harness G protein-coupled receptor signaling and trafficking, and have collectively opened new possibilities in G protein-coupled receptor drug discovery. Combining pharmacological chaperoning and biased agonism properties into a unique given molecule would be of high therapeutic interest in many human diseases resulting from G protein-coupled receptor mutation and misfolding. This strategy perfectly fits to congenital Nephrogenic Diabetes Insipidus which is a typical conformational disease. In most of the cases, it is associated to inactivating mutations of the renal arginine-vasopressin V2 receptor leading to misfolding and intracellular retention of the receptor, causing the inability of patients to concentrate their urine in response to the antidiuretic hormone. Cell-permeable pharmacological chaperones have been successfully challenged to restore plasma membrane localization of the receptor mutants and to rescue their function. Interestingly, different classes of pharmacological chaperones of the V2 receptor have proven their usefulness and efficacy, such as antagonists, agonists as well as biased agonists. These compounds, particularly small-molecule biased agonists which elicit the V2-induced Gs protein-dependent signaling pathway, but not V2-related arrestin-dependent cell responses, represent a potential therapeutic treatment of this X-linked genetic pathology.
       
  • Physicochemical determinants of antibody-protein interactions
    • Abstract: Publication date: Available online 19 November 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Murat Karadag, Merve Arslan, Nazli Eda Kaleli, Sibel KalyoncuAbstractAntibodies are specialized proteins generated by immune system for high specificity and affinity binding to target antigens. Because of their essential roles in immune system, antibodies have been successfully developed and engineered as biopharmaceuticals for treatment of various diseases. Analysis of antibody-protein interactions is always required to get detailed information on effectivity of such antibody-based therapeutics. Although physicochemical rules cannot be generalized for every antibody-protein interaction, there are some features which should be taken into account during antibody development and engineering efforts. In this chapter, physicochemical analysis of antibody paratope-protein epitope interactions will be discussed to highlight important characteristics. First, paratope and non-paratope regions of antibodies will be described and important roles of these regions on binding and biophysical features of antibodies will be discussed. Then, general features of epitope regions of protein antigens will be introduced along with several computational/experimental tools to identify them. Lastly, a rising star of antibody biopharmaceuticals, nanobodies, will be described to show importance of next-generation antibody fragment based biopharmaceuticals in drug development.
       
  • LOXL1 folding in exfoliation glaucoma
    • Abstract: Publication date: Available online 21 October 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Audrey M. Bernstein, Robert Ritch, J. Mario WolosinAbstractExfoliation syndrome (XFS) is an age-related disease defined by the deposition of aggregated fibrous material (XFM) in the peri-cellular space. Principal morbidity occurs in the eye, where XFM accumulates on the anterior ocular tissues. GWAS have found that certain genetic variants of lysyl oxidase-like 1 (LOXL1), a matrix cross-linking enzyme that is required for elastic fiber formation confer risk for the development of XFS, but are not a single causative factor as many genetically affected individuals do not develop XFS or subsequent glaucoma (XFG). We have found that XFG cells display defects in lysosomes, microtubules, autophagy, and mitochondria resembling defects found in cells from age-related syndromes, such as the main neurodegenerative diseases. In the majority of these diseases, the determining cellular factor is a protein containing intrinsically disordered regions (IDRs) and displaying a high propensity for aggregation. We have found that in XFG patient-derived cells, LOXL1 protein is actively subjected to autophagic clearance, suggesting that LOXL1 is undergoing aggregation. In silico analysis demonstrates that LOXL1's first 369 aa constitute an IDR with the highest disorder probability peak centering around the known risk positions. Experimentally, we have found over-expression of either unmodified LOXL1 or fluorescent chimeras preserving the well-structured N-terminus cause copious intracellular aggregation and that aggregation wanes when the high IDR peaks are deleted. Overall, our work suggests that XFS/G results from the aggregation of the LOXL1 protein coupled with a reduction of cellular proteostasis capabilities in aging, resulting in a chronic build-up of LOXL1-containing protein aggregates.
       
  • Influence of the reducing environment in the misfolding of wine proteins
    • Abstract: Publication date: Available online 19 October 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Paolo Ruzza, Claudia Honisch, Matteo Marangon, Andrea Curioni, Alan Bakalinsky, Simone VincenziAbstractWhile proteins are present in wine at low concentration, and are largely associated with undesirable haze formation in white wines, certain types or fractions make direct and indirect contributions to sensory quality and physical stability. The proteins found in wine represent a small subclass of the total pool of grape proteins that remain soluble in the non-physiological conditions of the wine matrix which is characterised by the presence of alcohol, high acidity, and relatively high levels of phenolic compounds. Although initially stable in these conditions, during storage of white and rosé wines proteins undergo changes leading to haze formation which is considered one of the most relevant non-microbiological defects, and which makes the wine commercially unacceptable. This phenomenon involves the two most abundant proteins present in wines: thaumatin-like proteins and chitinases, both belonging to pathogenesis-related proteins of the grape berry. Haze formation is often triggered by thermal fluctuations occurring during storage of white wines, although the presence of other non-protein-related factors seems to be necessary. Here, we review the characteristics of these two protein families and the factors that influence their solubility with a focus on the disulfide bonds reduction as a possible trigger for the onset of their aggregation.
       
  • Protein misfolding in endoplasmic reticulum stress with applications to
           renal diseases
    • Abstract: Publication date: Available online 23 September 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Samera Nademi, Jeffrey G. DickhoutAbstractProtein misfolding may be the result of a variety of different processes that disrupt the ability of a protein to form a thermodynamically stable tertiary structure that allows it to perform its proper function. In this chapter, we explore the nature of a protein's form that allows it to have a stable tertiary structure, and examine specific mutation that are known to occur in the coding regions of DNA that disrupt a protein's ability to be folded into a thermodynamically stable tertiary structure. We examine the consequences of these protein misfoldings in terms of the endoplasmic reticulum stress response and resulting unfolded protein response. These conditions are specifically related to renal diseases. Further, we explore novel therapeutics, pharmacological chaperones, that are being developed to alleviate the disease burden associated with protein misfolding caused by mutations. These interventions aim to stabilize protein folding intermediates and allow proper folding to occur as well as prevent protein aggregation and the resulting pathophysiological consequences.
       
  • Liquid-liquid phase transitions and amyloid aggregation in proteins
           related to cancer and neurodegenerative diseases
    • Abstract: Publication date: Available online 21 September 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Guilherme A.P. de Oliveira, Yraima Cordeiro, Jerson L. Silva, Tuane C.R.G. VieiraAbstractLiquid-liquid phase separation (LLPS) and phase transition (LLPT) of proteins and nucleic acids have emerged as a new paradigm in cell biology. Here we will describe the recent findings about LLPS and LLPT, including the molecular and physical determinants leading to their formation, the resulting functions and their implications in cell physiology and disease. Amyloid aggregation is implicated in many neurodegenerative diseases and cancer, and LLPS of proteins involved in these diseases appear to be related to their function in different cell contexts. Amyloid formation would correspond to an irreversible liquid-to-solid transition, as clearly observed in the case of PrP, TDP43, FUS/TLS and tau protein in neurodegenerative pathologies as well as with the mutant tumor suppressor p53 in cancer. Nucleic acids play a modulatory effect on both LLPS and amyloid aggregation. Understanding the molecular events regulating how the demixing process advances to solid-like fibril materials is crucial for the development of novel therapeutic strategies against cancer and neurodegenerative maladies.
       
  • Misfolded proteins as a therapeutic target in Alzheimer's disease
    • Abstract: Publication date: Available online 21 September 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): S. Imindu Liyanage, Donald F. WeaverAbstractFor decades, Alzheimer's Disease (AD) was defined as a disorder of protein misfolding and aggregation. In particular, the extracellular peptide fragment: amyloid-β (Aβ), and the intracellular microtubule-associated protein: tau, were thought to initiate a neurodegenerative cascade which culminated in AD's progressive loss of memory and executive function. As such, both proteins became the focus of intense scrutiny, and served as the principal pathogenic target for hundreds of clinical trials. However, with varying efficacy, none of these investigations produced a disease-modifying therapy – offering patients with AD little recourse aside from transient, symptomatic medications. The near universal failure of clinical trials is unprecedented for a major research discipline. In part, this has motivated an increasing skepticism of the relevance of protein misfolding to AD's etiology. Several recent observations, principally the presence of significant protein pathologies in non-demented seniors, have lent credence to an apparent cursory role for Aβ and tau. Herein, we review both Aβ and tau, examining the processes from their biosynthesis to their pathogenesis and evaluate their vulnerability to medicinal intervention. We further attempt to reconcile the apparent failure of trials with the potential these targets hold. Ultimately, we seek to answer if protein misfolding is a viable platform in the pursuit of a disease-arresting strategy for AD.
       
  • Cytotoxic species in amyloid-associated diseases: Oligomers or mature
           fibrils
    • Abstract: Publication date: Available online 7 August 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Mohammad Khursheed Siddiqi, Sadia Malik, Nabeela Majid, Parvez Alam, Rizwan Hasan KhanAbstractAmyloid diseases especially, Alzheimer's disease (AD), is characterized by an imbalance between the production and clearance of amyloid-β (Aβ) species. Amyloidogenic proteins or peptides can transform structurally from monomers into β-stranded fibrils via multiple oligomeric states. Among various amyloid species, structured oligomers are proposed to be more toxic than fibrils; however, the identification of amyloid oligomers has been challenging due to their heterogeneous and metastable nature. Multiple techniques have recently helped in better understanding of oligomer's assembly details and structural properties. Moreover, some progress on elucidating the mechanisms of oligomer-triggered toxicity has been made. Based on the collection of current findings, there is growing consensus that control of toxic amyloid oligomers could be a valid approach to regulate amyloid-associated toxicity, which could advance development of new diagnostics and therapeutics for amyloid-related diseases. In this review, we have described the recent scenario of amyloid diseases with a great deal of information about the recent understanding of oligomers' assembly, structural properties, and toxicity. Also comprehensive details have been provided to differentiate the degree of toxicity associated with prefibrillar aggregates.
       
  • Sleep deprivation, oxidative stress and inflammation
    • Abstract: Publication date: Available online 24 April 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Fatin Atrooz, Samina SalimAbstractAdequate sleep is essential for normal brain function, especially during early life developmental stages as postnatal brain maturation occurs during the critical period of childhood and adolescence. Therefore, sleep disturbance and/or deficit during this period can have detrimental consequences. Many epidemiological and clinical studies have linked early life sleep disturbance with occurrence of later life behavioral and cognitive impairments. Role of oxidative stress and inflammation has been implicated in sleep deprivation-related impairments. This review article presents a detailed description of the current state of the literature on the subject.
       
  • Biological functions and clinical implications of interleukin-34 in
           inflammatory diseases
    • Abstract: Publication date: Available online 8 March 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Yun Ge, Man Huang, Xiao-mei Zhu, Yong-ming YaoAbstractInterleukin (IL)-34 is a recently discovered cytokine and ligand of the colony-stimulating factor (CSF)-1 receptor. Although CSF-1 and IL-34 share similar biological properties, their expression patterns and downstream signaling pathways are distinct. IL-34 can influence differentiation and has functions in multiple cell types (e.g., dendritic cells, monocytes, macrophages). In the pathological conditions, IL-34 is induced by pro-inflammatory stimuli (e.g., cytokines, pathogen-associated molecular patterns, and infection). Current evidence shows that IL-34 is a critical player in inflammatory response and is involved in the pathogenesis of inflammatory autoimmune dysfunction. Therefore, IL-34 may be a promising clinical biomarker and therapeutic target for treating inflammatory related disorders. In this article, we review the advances in biological functions of IL-34 and our understanding of its role in the development of inflammatory diseases as well as therapeutic applications.
       
 
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