Limited proteolysis of NACP/alpha-synuclein

The NAC region of NACP/alpha-synuclein is a secondary component of Alzheimer's disease amyloid. alpha-Synuclein is a major component of Lewy bodies, a typical neuropathological feature of Parkinson's disease. However, the physiological role and deposition mechanisms of alpha-synuclein are unknown. Structural analyses of alpha-synuclein should provide a better understanding of its biochemical characteristics. We investigated the digestion of alpha-synuclein withalpha-chymotrypsin and cathepsin D, which are reported to be involved in amyloidogenesis, under various conditions in vitro. There are many putative cleavage sites for these enzymes in alpha-synuclein, including in the NAC region. However, most of the predicted sites remained undigested, and the NAC region was found to be intact even after extensive digestion. This peculiar characteristic of alpha-synuclein may be relevant to the abnormal deposition of this molecule in alpha-synuclein-associated neurodegenerative diseases.