title: Tau degradation: the ubiquitin-proteasome system versus the autophagy-lysosome system.
abstract: The ubiquitin-proteasome system (UPS) and the autophagy-lysosome system are two major protein quality control mechanisms in eukaryotic cells. While the UPS has been considered for decades as the critical regulator in the degradation of various aggregate-prone proteins, autophagy has more recently been shown to be an important pathway implicated in neuronal health and disease. The two hallmark lesions of Alzheimer's disease (AD) are extracellular β-amyloid plaques and intracellular tau tangles. It has been suggested that tau accumulation is pathologically more relevant to the development of neurodegeneration and cognitive decline in AD patients than β-amyloid plaques. Here, we review the UPS and autophagy-mediated tau clearance mechanisms and outline the biochemical connections between these two processes. In addition, we discuss pharmacological methods that target these degradation systems for the treatment and prevention of AD.
authors.affiliation: Department of Applied Chemistry, College of Applied Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 446-701, Republic of Korea. mjlee@khu.ac.kr
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Lee
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Lee
authors.forename: David C
authors.initials: DC
authors.lastname: Rubinsztein
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D016875:tau Proteins; D046988:Proteasome Endopeptidase Complex