Multifaceted Regulation of ALDH1A1 by Cdk5 in Alzheimer's Disease Pathogenesis.

ABSTRACT: This study revealed multifaceted regulation of ALDH1A1 by Cdk5 in Alzheimer's disease (AD) pathogenesis. ALDH1A1 is a multifunctional enzyme with dehydrogenase, esterase, and anti-oxidant activities. ALDH1A1 is also a major regulator of retinoic acid (RA) signaling, which is critical for normal brain homeostasis. We identified ALDH1A1 as both physiological and pathological target of Cdk5. First, under neurotoxic conditions, Cdk5-induced oxidative stress upregulates ALDH1A1 transcription. Second, Cdk5 increases ALDH1A1 levels by preventing its ubiquitylation via direct phosphorylation. Third, ALDH1A1 phosphorylation increases its dehydrogenase activity by altering its tetrameric state to a highly active monomeric state. Fourth, persistent oxidative stress triggered by deregulated Cdk5 inact

SUBMITTER: Nikhil K 

PROVIDER: S-EPMC6368892 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature