Dual-target inhibitors of cholinesterase and GSK-3ß to modulate Alzheimer's disease.
Drug Discov Today
; 29(4): 103914, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38340951
ABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disease that affects over 55 million patients worldwide. Most of the approved small-molecule drugs for AD have been designed to tackle a single pathological hallmark, such as cholinergic dysfunction or amyloid toxicity, and thus may not fully address the multifactorial nature of the disease. Inhibition of both cholinesterase and glycogen synthase kinase-3ß (GSK-3ß) has emerged as a promising strategy to modulate AD. However, the dual inhibition of these two targets posts challenges in molecular design:
issues related to target engagements and biopharmaceutical properties in particular must be overcome. In this review, we discuss the physiopathological roles and structures of cholinesterase and GSK-3ß as well as recently reported dual-target inhibitors. We critically evaluate the current status of the discovery of dual-target inhibitors of cholinesterase and GSK-3ß, and highlight further perspectives.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Enfermedades Neurodegenerativas
/
Enfermedad de Alzheimer
Límite:
Humans
Idioma:
En
Revista:
Drug Discov Today
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2024
Tipo del documento:
Article
País de afiliación:
China