Computational Screening of Repurposed Drugs for HMG-CoA Synthase 2 in Alzheimer's Disease.
J Alzheimers Dis
; 100(2): 475-485, 2024.
Article
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| MEDLINE
| ID: mdl-38875044
ABSTRACT
Background:
HMGCS2 (mitochondrial 3-hydroxy-3-methylglutaryl-COA synthase 2) plays a pivotal role as a control enzyme in ketogenesis, and its association with the amyloid-ß protein precursor (AßPP) in mitochondria implicates a potential involvement in Alzheimer's disease (AD) pathophysiology.Objective:
Our study aimed at identifying repurposed drugs using the DrugBank database capable of inhibiting HMGCS2 activity.Methods:
Exploiting the power of drug repurposing in conjunction with virtual screening and molecular dynamic (MD) simulations against 'HMGCS2', we present new in-silico insight into structure-based drug repurposing.Results:
The initial molecules were screened for their binding affinity to HMGCS2. Subsequent interaction analyses and extensive 300âns MD simulations were conducted to explore the conformational dynamics and stability of HMGCS2 in complex with the screened molecules, particularly Penfluridol and Lurasidone.Conclusions:
The study revealed that HMGCS2 forms stable protein-ligand complexes with Penfluridol and Lurasidone. Our findings indicate that Penfluridol and Lurasidone competitively bind to HMGCS2 and warrant their further exploration as potential repurposed molecules for anti-Alzheimer's drug development.Palabras clave
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Base de datos:
MEDLINE
Asunto principal:
Reposicionamiento de Medicamentos
/
Enfermedad de Alzheimer
/
Hidroximetilglutaril-CoA Sintasa
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2024
Tipo del documento:
Article