Computer-Aided Drug Design of ß-Secretase, γ-Secretase and Anti-Tau Inhibitors for the Discovery of Novel Alzheimer's Therapeutics.
Int J Mol Sci
; 21(3)2020 Jan 21.
Article
em En
| MEDLINE
| ID: mdl-31973122
ABSTRACT
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-ß 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 ß-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 ß-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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Desenho de Fármacos
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Secretases da Proteína Precursora do Amiloide
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Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article