4-Acyl-3,4-dihydropyrrolo[1,2-a]pyrazine Derivative Rescued the Hippocampal-Dependent Cognitive Decline of 5XFAD Transgenic Mice by Dissociating Soluble and Insoluble Aß Aggregates.
ACS Chem Neurosci
; 14(11): 2016-2026, 2023 06 07.
Article
em En
| MEDLINE
| ID: mdl-37171100
ABSTRACT
Cerebral amyloid-ß (Aß) deposition is a representative hallmark of Alzheimer's disease (AD). Development of Aß-clearing small molecules could be an advantageous therapeutic strategy for Aß clearance considering the advantages in terms of side effects, cost-effectiveness, stability, and oral bioavailability. Here, we report an Aß-dissociating small molecule, YIAD-0121, a derivative of 4-acyl-3,4-dihydropyrrolo[1,2-a]pyrazine. Through a series of anti-Aß screening assays, YIAD-0121 was identified to inhibit Aß aggregation and dissociate preformed Aß fibrils in vitro. Furthermore, the administration of YIAD-0121 in 5XFAD transgenic AD mice inhibited the increase of cerebral Aß aggregation and progression of hippocampus-dependent cognitive decline, with ameliorated neuroinflammation.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Alzheimer
/
Disfunção Cognitiva
Limite:
Animals
Idioma:
En
Revista:
ACS Chem Neurosci
Ano de publicação:
2023
Tipo de documento:
Article