The yeast Saccharomyces cerevisiae has proven to be a useful model system to investigate the mechanism of prion generation and inheritance, to which studies in Sup35 made a great contribution. Recent studies demonstrated that 'protein misfolding and aggregation' (i.e. amyloidogenesis) is a common principle underlying the pathogenesis of neurodegenerative diseases including prion, amyotrophic lateral sclerosis (ALS), Perkinson's (PD), Alzheimer's (AD) diseases and polyglutamine (polyQ) diseases such as spinocerebellar ataxia (SCA) and Hantington's disease (HD). By these findings, the yeast has again been drawing increased attention as a useful system for studying neurodegenerative proteinopathies. So far, it has been reported that proteolytic cleavage of causative amyloidogenic proteins might affect the pathogenesis of the respective neurodegenerative diseases. Although those reports provide a clear phenomenological description, in the majority of cases, it has remained elusive if proteolysis is directly involved in the pathogenesis of the diseases. Recently, we have demonstrated in yeast that proteolysis suppresses prion generation. The yeast-based strategy might make a breakthrough to the unsolved issues.
Keywords: APP; Amyloid; HTT; PrA-PrB; Sup35; TDP-43; neurodegenerative disease; prion; proteolysis.