TGR5 deficiency in excitatory neurons ameliorates Alzheimer's pathology by regulating APP processing.
Sci Adv
; 10(26): eado1855, 2024 Jun 28.
Article
em En
| MEDLINE
| ID: mdl-38941459
ABSTRACT
Bile acids (BAs) metabolism has a significant impact on the pathogenesis of Alzheimer's disease (AD). We found that deoxycholic acid (DCA) increased in brains of AD mice at an early stage. The enhanced production of DCA induces the up-regulation of the bile acid receptor Takeda G protein-coupled receptor (TGR5), which is also specifically increased in neurons of AD mouse brains at an early stage. The accumulation of exogenous DCA impairs cognitive function in wild-type mice, but not in TGR5 knockout mice. This suggests that TGR5 is the primary receptor mediating these effects of DCA. Furthermore, excitatory neuron-specific knockout of TGR5 ameliorates Aß pathology and cognition impairments in AD mice. The underlying mechanism linking TGR5 and AD pathology relies on the downstream effectors of TGR5 and the APP production, which is succinctly concluded as a "p-STAT3-APH1-γ-secretase" signaling pathway. Our studies identified the critical role of TGR5 in the pathological development of AD.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Precursor de Proteína beta-Amiloide
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Receptores Acoplados a Proteínas G
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Doença de Alzheimer
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Neurônios
Limite:
Animals
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Humans
Idioma:
En
Revista:
Sci Adv
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China