Inhibition of caspase-1 ameliorates tauopathy and rescues cognitive impairment in SAMP8 mice.
Metab Brain Dis
; 37(4): 1197-1205, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35143023
ABSTRACT
The inflammasome assembles leading to increased cleavage and activity of caspase-1 and downstream IL-1ß release, which plays a significant role in the pathogenesis of Alzheimer's disease (AD). Previous studies have shown that caspase-1-mediated neuroinflammation occurs early in AD process. However, the detailed role of caspase-1 in aging-related AD-like neuropathology is still unclear so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we detected the levels of caspase-1 in brains of 3-, 7-, and 11-month-old mice and observed that caspase-1 was activated during aging process. More importantly, we provided the evidence that VX-765, a selective inhibitor of caspase-1, significantly rescued spatial learning and memory impairments and reduced tau hyperphosphorylation in brains of SAMP8 mice at early stages of the disease. This amelioration might be attributed to IL-1ß-induced hypoactivation of tau kinases. Our results imply that caspase-1 may represent as a potential therapeutic target for neurodegenerative tauopathies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Caspase 1
/
Tauopatias
/
Doença de Alzheimer
/
Disfunção Cognitiva
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article