Chaperone mediated degradation of aggregated alpha synuclein

Aggregation and cytotoxicity of misfolded alpha-synuclein is postulated to be crucial in the disease process of neurodegenerative disorders such as Parkinson's disease and dementia with Lewy bodies. Overexpression of C-terminally modified alpha-synuclein and synphilin-1 produce intracellular alpha-synuclein aggregates in human H4 cells (McLean et al., Neuroscience, 2001). We have previously demonstrated that overexpression of heat shock protein 70 (Hsp70) dramatically reduces the number of alpha-synuclein aggregates in a cell culture model (McLean et al., J. Neurochem., 2002), and Hsp70 has also been shown to pr…