AUTHOR=Hartz Anika M. S. , Zhong Yu , Shen Andrew N. , Abner Erin L. , Bauer Björn TITLE=Preventing P-gp Ubiquitination Lowers Aβ Brain Levels in an Alzheimer’s Disease Mouse Model JOURNAL=Frontiers in Aging Neuroscience VOLUME=10 YEAR=2018 URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2018.00186 DOI=10.3389/fnagi.2018.00186 ISSN=1663-4365 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 patients are increased compared to capillaries isolated from brain tissue of cognitive normal individuals. We extended this line of research to