Computer-Aided Drug Design of β-Secretase, γ-Secretase and Anti-Tau Inhibitors for the Discovery of Novel Alzheimer’s Therapeutics
| Autor: | Antreas Afantitis, Lefteris C. Zacharia, Varnavas D. Mouchlis, Georgia Melagraki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Protein Conformation
Druggability Plaque Amyloid Review γ-secretase Ligands lcsh:Chemistry Aspartic Acid Endopeptidases β-secretase tau Phosphorylation qsar computer-aided drug design lcsh:QH301-705.5 Spectroscopy medicine.diagnostic_test Brain cheminformatics Neurodegenerative Diseases Neurofibrillary Tangles alzheimer’s disease General Medicine Human brain Small molecule Computer Science Applications Molecular Docking Simulation medicine.anatomical_structure Cheminformatics Proteolysis tau Proteins Molecular Dynamics Simulation Biology Catalysis Inorganic Chemistry Alzheimer Disease medicine Animals Humans Physical and Theoretical Chemistry computational ligand-based design Molecular Biology Organic Chemistry molecular docking molecular dynamics Review article lcsh:Biology (General) lcsh:QD1-999 Drug Design Amyloid Precursor Protein Secretases computational structure-based design Neuroscience Function (biology) |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 3, p 703 (2020) International Journal of Molecular Sciences |
| ISSN: | 1422-0067 |
| Popis: | Aging-associated neurodegenerative diseases, which are characterized by progressive neuronal death and synapses loss in human brain, are rapidly growing affecting millions of people globally. Alzheimer’s is the most common neurodegenerative disease and it can be caused by genetic and environmental risk factors. This review describes the amyloid-β and Tau hypotheses leading to amyloid plaques and neurofibrillary tangles, respectively which are the predominant pathways for the development of anti-Alzheimer’s small molecule inhibitors. The function and structure of the druggable targets of these two pathways including β-secretase, γ-secretase, and Tau are discussed in this review article. Computer-Aided Drug Design including computational structure-based design and ligand-based design have been employed successfully to develop inhibitors for biomolecular targets involved in Alzheimer’s. The application of computational molecular modeling for the discovery of small molecule inhibitors and modulators for β-secretase and γ-secretase is summarized. Examples of computational approaches employed for the development of anti-amyloid aggregation and anti-Tau phosphorylation, proteolysis and aggregation inhibitors are also reported. |
| Databáze: | OpenAIRE |
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