VPS35 regulates tau phosphorylation and neuropathology in tauopathy.

ABSTRACT: The vacuolar protein sorting 35 (VPS35) is a major component of the retromer recognition core complex which regulates intracellular protein sorting and trafficking. Deficiency in VPS35 by altering APP/Aβ metabolism has been linked to late-onset Alzheimer's disease. Here we report that VPS35 is significantly reduced in Progressive Supra-nuclear Palsy and Picks' disease, two distinct primary tauopathies. In vitro studies show that overexpression of VPS35 leads to a reduction of pathological tau in neuronal cells, whereas genetic silencing of VPS35 results in its accumulation. Mechanistically the availability of active cathepsin D mediates the effect of VPS35 on pathological tau accumulation. Moreover, in a relevant transgenic mouse model of tauopathy, down-regulation of VPS35 results in an e

SUBMITTER: Vagnozzi AN 

PROVIDER: S-EPMC6949432 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature