Dysfunction of X-linked inhibitor of apoptosis protein (XIAP) triggers neuropathological processes via altered p53 activity in Huntington's disease.

ABSTRACT: Mitochondrial dysfunction is associated with neuronal damage in Huntington's disease (HD), but the precise mechanism of mitochondria-dependent pathogenesis is not understood yet. Herein, we found that colocalization of XIAP and p53 was prominent in the cytosolic compartments of normal subjects but reduced in HD patients and HD transgenic animal models. Overexpression of mutant Huntingtin (mHTT) reduced XIAP levels and elevated mitochondrial localization of p53 in striatal cells in vitro and in vivo. Interestingly, XIAP interacted directly with the C-terminal domain of p53 and decreased its stability via autophagy. Overexpression of XIAP prevented mitochondrially targeted-p53 (Mito-p53)-induced mitochondrial oxidative stress and striatal cell death, whereas, knockdown of XIAP exacerbated Mi

SUBMITTER: Hyeon SJ 

PROVIDER: S-EPMC8364511 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature