Failure of DNA double-strand break repair by tau mediates Alzheimer's disease pathology in vitro.
Commun Biol
; 5(1): 358, 2022 04 13.
Article
em En
| MEDLINE
| ID: mdl-35418705
ABSTRACT
DNA double-strand break (DSB) is the most severe form of DNA damage and accumulates with age, in which cytoskeletal proteins are polymerized to repair DSB in dividing cells. Since tau is a microtubule-associated protein, we investigate whether DSB is involved in tau pathologies in Alzheimer's disease (AD). First, immunohistochemistry reveals the frequent coexistence of DSB and phosphorylated tau in the cortex of AD patients. In vitro studies using primary mouse cortical neurons show that non-p-tau accumulates perinuclearly together with the tubulin after DSB induction with etoposide, followed by the accumulation of phosphorylated tau. Moreover, the knockdown of endogenous tau exacerbates DSB in neurons, suggesting the protective role of tau on DNA repair. Interestingly, synergistic exposure of neurons to microtubule disassembly and the DSB strikingly augments aberrant p-tau aggregation and apoptosis. These data suggest that DSB plays a pivotal role in AD-tau pathology and that the failure of DSB repair leads to tauopathy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tauopatias
/
Doença de Alzheimer
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Japão