The role of the ubiquitin-proteasomal pathway in Parkinson's disease and other neurodegenerative disorders

A unifying feature of neurodegenerative diseases is the abnormal accumulati on and processing of mutant or damaged, intra- and extracellular proteins; this leads to selective neuronal vulnerability and dysfunction. The ubiquit in-proteasomal pathway (UPP) is poised to play a central role in the proces sing of damaged and toxic proteins by Libiquitin-dependent proteolysis. The UPP can be overwhelmed in several neurodegenerative diseases. This results in the accumulation of toxic proteins and the formation of inclusions, and ultimately to neuronal dysfunction and cell death. Further analysis of the cellular and molecular mechanisms by which the UPP influences the detoxifi cation of damaged and toxic proteins in neurodegenerative diseases could pr ovide novel concepts and targets for the treatment and understanding of the pathogenesis of these devastating disorders.