Endolysosomal degradation of Tau and its role in glucocorticoid-driven hippocampal malfunction.

ABSTRACT: Emerging studies implicate Tau as an essential mediator of neuronal atrophy and cognitive impairment in Alzheimer's disease (AD), yet the factors that precipitate Tau dysfunction in AD are poorly understood. Chronic environmental stress and elevated glucocorticoids (GC), the major stress hormones, are associated with increased risk of AD and have been shown to trigger intracellular Tau accumulation and downstream Tau-dependent neuronal dysfunction. However, the mechanisms through which stress and GC disrupt Tau clearance and degradation in neurons remain unclear. Here, we demonstrate that Tau undergoes degradation via endolysosomal sorting in a pathway requiring the small GTPase Rab35 and the endosomal sorting complex required for transport (ESCRT) machinery. Furthermore, we find that GC i

SUBMITTER: Vaz-Silva J 

PROVIDER: S-EPMC6187216 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature