Assessment of Impaired Proteasomal Function in a Cellular Model of Polyglutamine Diseases

A protein marked for degradation by the ubiquitin-proteasome pathway (UPP) is attached to multiple molecules of ubiquitin, a 76-amino-acid protein that targets the protein for rapid hydrolysis by 26S proteasome. Impaired function of UPP results in accumulation of misfolded and ubiquitinated proteins and has been implicated in the pathogenesis of various neurodegenerative diseases, including polyglutamine diseases. Impaired function of UPP can be evaluated either by assaying the proteasome’s protease activity or the accumulation of ubiquitinated proteins.