| Author | Search for: Dufty, B.; Search for: Warner, L.; Search for: Hou, S.; Search for: Jiang, S.; Search for: Gomez-Isla, T.; Search for: Leenhouts, K.; Search for: Oxford, J.; Search for: Feany, M.; Search for: Masliah, E.; Search for: Rohn, T. |
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| Format | Text, Article |
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| Subject | aged; alpha-synuclein; antibody; area under curve; blotting, western; brain; Calpain; cell line, tumor; disease; drosophila; female; fluorescent antibody technique; immunohistochemistry; immunoprecipitation; ischemia; Lewy body disease; male; metabolism; mice; mice, inbred C57BL; mice, transgenic; middle aged; model; neurons; Parkinson disease; pathology; protease; protein structure, secondary; state; structure |
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| Abstract | Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are both characterized pathologically by the presence of neuronal inclusions termed Lewy bodies (LBs). A common feature found in LBs are aggregates of alpha-synuclein (alpha-Syn), and although it is now recognized that alpha-Syn is the major building block for these toxic filaments, the mechanism of how this occurs remains unknown. In the present study, we demonstrate that proteolytic processing of alpha-Syn by the protease calpain I leads to the formation of aggregated high-molecular weight species and adoption of a beta-sheet structure. To determine whether calpain-cleavage of alpha-Syn occurs in PD and DLB, we designed site-directed calpain-cleavage antibodies to alpha-Syn and tested their utility in several animal model systems. Detection of calpain-cleaved alpha-Syn was evident in mouse models of cerebral ischemia and PD and in a Drosophila model of PD. In the human PD and DLB brain, calpain-cleaved alpha-Syn antibodies immunolabeled LBs and neurites in the substantia nigra. Moreover, calpain-cleaved alpha-Syn fragments identified within LBs colocalized with activated calpain in neurons of the PD and DLB brains. These findings suggest that calpain I may participate in the disease-linked aggregation of alpha-Syn in various alpha-synucleinopathies |
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| Publication date | 2007-05 |
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| In | |
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| Language | English |
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| NRC number | DUFTY2007 |
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| NPARC number | 9370012 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 0a618bee-a178-433e-8b61-3b25c31f363d |
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| Record created | 2009-07-10 |
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| Record modified | 2020-05-10 |
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