FOXO protects against age-progressive axonal degeneration.

ABSTRACT: Neurodegeneration resulting in cognitive and motor impairment is an inevitable consequence of aging. Little is known about the genetic regulation of this process despite its overriding importance in normal aging. Here, we identify the Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of neuronal integrity by inhibiting age-progressive axonal degeneration in mammals. FOXO expression progressively increased in aging human and mouse brains. The nervous system-specific deletion of Foxo transcription factors in mice accelerates aging-related axonal tract degeneration, which is followed by motor dysfunction. This accelerated neurodegeneration is accompanied by levels of white matter astrogliosis and microgliosis in middle-aged Foxo knockout mice that are typically onl

SUBMITTER: Hwang I 

PROVIDER: S-EPMC5771393 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature