Autophagy-Dependent Increased ADAM10 Mature Protein Induced by TFEB Overexpression Is Mediated Through PPARα.

ABSTRACT: Nonamyloidogenic processing of amyloid precursor protein (APP) by augmenting ADAM10 is a promising therapeutic strategy for Alzheimer's disease (AD). Therefore identification of molecular pathways that regulate ADAM10 expression is crucial. Autophagy is strongly dysregulated in AD, and TFEB was recently shown to be a master regulator of autophagy-lysosome pathway (ALP). Here, we report that TFEB expression in HeLa cells increased ADAM10 mature form by 72% (p < 0.01, n = 4), while TFEB knockdown by CRISPR strategy reduced ADAM10 mature form by 36% (p < 0.05, n = 4). Autophagy inhibition by 3-methyladenine (3-MA), but not bafilomycin A1 (BAF1), reduced ADAM10 mature form by 49% (p < 0.05, n = 4) in the TFEB expressing HeLa cells. Autophagy activation by 3 h of starvation increased ADAM10 to

SUBMITTER: Wang H 

PROVIDER: S-EPMC8026501 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature