JAB1 deletion in oligodendrocytes causes senescence-induced inflammation and neurodegeneration in mice.

ABSTRACT: Oligodendrocytes are the primary target of demyelinating disorders, and progressive neurodegenerative changes may evolve in the CNS. DNA damage and oxidative stress are considered key pathogenic events, but the underlying molecular mechanisms remain unclear. Moreover, animal models do not fully recapitulate human diseases, complicating the path to effective treatments. Here we report that mice with cell-autonomous deletion of the nuclear COP9 signalosome component CSN5 (JAB1) in oligodendrocytes develop DNA damage and defective DNA repair in myelinating glial cells. Interestingly, oligodendrocytes lacking JAB1 expression underwent a senescence-like phenotype that fostered chronic inflammation and oxidative stress. These mutants developed progressive CNS demyelination, microglia inflammatio

SUBMITTER: Rivellini C 

PROVIDER: S-EPMC8803330 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature