Affiliations: [a] Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Hachioji, Tokyo 192-0364, Japan | [b] Department of Neural Plasticity, Tokyo Institute of Psychiatry, Setagaya-ku, Tokyo 156-8585, Japan
Correspondence:
[***]
Corresponding author: Dr. Kenji Uéda, Department of Neural Plasticity, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan. Tel.: +81 3 3304 5701, ext. 511; Fax: +81 3 3329 8035; E-mail: kenueda@prit.go.jp
Note: [*] This two authors contributed equally to this work.
Note: [**] Present address: Division of Demyelinating Disease and Aging, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan.
Abstract: The NAC region of NACP/α-synuclein is a secondary component of Alzheimer's disease amyloid. α-Synuclein is a major component of Lewy bodies, a typical neuropathological feature of Parkinson's disease. However, the physiological role and deposition mechanisms of α-synuclein are unknown. Structural analyses of α-synuclein should provide a better understanding of its biochemical characteristics. We investigated the digestion of α-synuclein withα-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 α-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 α-synuclein may be relevant to the abnormal deposition of this molecule in α-synuclein-associated neurodegenerative diseases.
