Preventing P-gp Ubiquitination Lowers Aβ Brain Levels in an Alzheimer's Disease Mouse Model.

ABSTRACT: One characteristic of Alzheimer's disease (AD) is excessive accumulation of amyloid-β (Aβ) in the brain. Aβ brain accumulation is, in part, due to a reduction in Aβ clearance from the brain across the blood-brain barrier. One key element that contributes to Aβ brain clearance is P-glycoprotein (P-gp) that transports Aβ from brain to blood. In AD, P-gp protein expression and transport activity levels are significantly reduced, which impairs Aβ brain clearance. The mechanism responsible for reduced P-gp expression and activity levels is poorly understood. We recently demonstrated that Aβ₄₀ triggers P-gp degradation through the ubiquitin-proteasome pathway. Consistent with these data, we show here that ubiquitinated P-gp levels in brain capillaries isolated from brain samples of AD

SUBMITTER: Hartz AMS 

PROVIDER: S-EPMC6028735 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature