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.