Protein quality control in Alzheimer's disease by the ubiquitin proteasome system.
The ubiquitin proteasome system (UPS) is the major protein quality control system in eukaryotic cells. Many neurodegenerative diseases are characterized by aggregates and inclusions of aberrant proteins, implying a sub-optimal functioning or defective UPS. The last few years have seen increasing evidence for the involvement of the UPS in neurodegenerative disorders, including Alzheimer's disease (AD). Notably, decreases in proteasome activity were detected in several cortical areas in AD patients. In addition, proteins that accumulate in the classical hallmarks of AD were linked to UPS function. This review specifically discusses the involvement of the UPS in AD pathogenesis. First, a detailed overview of the UPS is presented, after which AD pathology and its relation to the UPS is discussed.
de Vrij
F M S
FM
Netherlands Institute for Brain Research, Graduate School for Neurosciences, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands. f.devrij@erasmusmc.nl
Fischer
D F
DF
van Leeuwen
F W
FW
Hol
E M
EM
D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D006801:Humans; D007858:Learning / Q000502:physiology; D009154:Mutation; D018384:Oxidative Stress / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000145:classification / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D025801:Ubiquitin / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D025801:Ubiquitin; D016875:tau Proteins; D046988:Proteasome Endopeptidase Complex