Disrupted ubiquitin proteasome system underlying tau accumulation in Alzheimer's disease

Accumulation of phosphorylated tau (p-tau) has long been an underappreciated hallmark of Alzheimer's disease. Tau is one of the major components of microtubule networks in neurons, and its abnormal phosphorylation and aggregation are closely related to the impairment of axonal transport. Abnormalities in axonal transport can impede autophagy in neurons, interrupting the autophagic clearance of amyloid beta. The ubiquitin proteasome system (UPS) maintains intracellular proteostasis by degrading abnormal or redundant proteins. Ever-mounting evidence suggests that UPS deficits contribute to p-tau accumulation. And targeting UPS attenuates tau pathology. This review endeavors to exam the potential role of UPS in p-tau aggregation, and how pathogenic tau may inflict other abnormalities such as amyloid beta accumulation in Alzheimer's disease. (C) 2020 Elsevier Inc. All rights reserved.

Automated summary

This article discusses the importance of phosphorylated tau in Alzheimer's disease, as well as the critical role of the ubiquitin proteasome system in regulating this process, revealing the close relationship between the two.