TSPO deficiency accelerates amyloid pathology and neuroinflammation by impairing microglial phagocytosis.
Neurobiol Aging
; 106: 292-303, 2021 10.
Article
em En
| MEDLINE
| ID: mdl-34340010
ABSTRACT
Increasing evidence has placed inflammation and immune dysfunction at the center of the pathogenesis of Alzheimer's disease (AD). The mitochondrial protein translocator protein (18 kDa) (TSPO) is highly upregulated in microglia and astrocytes in response to inflammatory stimulation. However, the biological action of TSPO in the pathogenesis of AD has not been determined to date. In this study, we showed that TSPO expression was upregulated in brain tissues from AD patients and AD model mice. APP/PS1 mice lacking TSPO generated significantly higher levels of Aß1-40 and Aß1-42 peptides and more Aß plaques, as well as enhanced microglial activation, in the brain. TSPO-deficient microglia cultured in vitro showed a significant decrease in the ability to phagocytose Aß peptides or latex beads and generated more proinflammatory cytokines (TNF-α and IL-1ß) in response to Aß peptides. Our findings suggest that TSPO has protective functions against neuroinflammation and Aß pathogenesis in AD. TSPO may be a potential drug target for the development of drugs that have therapeutic or preventive effects in neuroinflammatory diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fagocitose
/
Encéfalo
/
Expressão Gênica
/
Regulação para Cima
/
Receptores de GABA
/
Microglia
/
Doença de Alzheimer
/
Doenças Neuroinflamatórias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China