A neurodegeneration checkpoint mediated by REST protects against the onset of Alzheimer's disease.

ABSTRACT: Many aging individuals accumulate the pathology of Alzheimer's disease (AD) without evidence of cognitive decline. Here we describe an integrated neurodegeneration checkpoint response to early pathological changes that restricts further disease progression and preserves cognitive function. Checkpoint activation is mediated by the REST transcriptional repressor, which is induced in cognitively-intact aging humans and AD mouse models at the onset of amyloid β-protein (Aβ) deposition and tau accumulation. REST induction is mediated by the unfolded protein response together with β-catenin signaling. A consequence of this response is the targeting of REST to genes involved in key pathogenic pathways, resulting in downregulation of gamma secretase, tau kinases, and pro-apoptotic proteins. Deleti

SUBMITTER: Aron L 

PROVIDER: S-EPMC10622455 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature