Abstract
Abnormal biology of α-synuclein (α-Syn) is directly implicated in the pathogenesis of Parkinson's disease and other α-synucleinopathies. Herein, we demonstrate that C-terminally truncated α-Syn (α-SynΔC), enriched in the pathological α-Syn aggregates, is normally generated from full-length α-Syn independent of α-Syn aggregation in brains and in cultured cells. The accumulation of α-SynΔC is enhanced in neuronal cells as compared with nonneuronal cells. Significantly, the expression of familial Parkinson's disease-linked mutant α-Syn is associated with the enhanced cellular accumulation of α-SynΔC Moreover, substoichiometric amounts of α-SynΔC enhance the in vitro aggregation of the more abundant full-length α-Syn. Finally, cases of a-synucleinopathy exhibit increases in the total soluble α-Syn and a higher proportion of soluble α-SynΔC, a condition favoring the aggregation of α-Syn. Collectively, our results indicate that the biology behind the generation and accumulation of α-SynΔC is likely to have relevance for the initiation and the progression of α-Syn aggregation in vivo.
Original language | English (US) |
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Pages (from-to) | 2162-2167 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 102 |
Issue number | 6 |
DOIs | |
State | Published - Feb 8 2005 |
Keywords
- Lewy body
- Mass spectrometry
- Proteolysis
- α-synucleinopathy