[Regulation of the protein degradation pathway by the ubiquitin family: its implication in neurodegenerative diseases].

Growing lines of evidence suggest that the neurodegenerative diseases are tightly linked to the ubiquitin and the proteasome pathway (UPP), which plays a pivotal role in selective protein degradation in the cells. Genetic mutations in the ubiquitin pathway (ie; parkin and Uchll) cause familial Parkinson's disease (PD), and sequestration of such UPP enzymes in the inclusion bodies are observed in not only sporadic forms of PD but also in other neurodegenerative diseases. These evidences place the reduction of UPP as a central mechanism underlying the pathogenesis and progression of neurodegenerative diseases linked to inclusion body formation. In addition to the UPP, autophagic pathway (AP), which is regulated by the ubiquitin-like modifier systems, attracted considerable attention as an alternative pathway to clean-up inclusion bodies in the cells. This review highlighted the recent progress in our understanding on the regulation of UPP and its cooperation with AP for the quality control of the proteins and elimination of ubiquitin positive aggregates.