Journal
FEBS LETTERS
Volume 587, Issue 18, Pages 3135-3141Publisher
WILEY
DOI: 10.1016/j.febslet.2013.07.053
Keywords
Parkinson's disease; Alpha-synuclein; Cyclin-dependent kinase 5; Phosphorylation; p35; Calpain
Funding
- National Science Centre [DEC-2012/05/B/NZ3/02047]
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Extracellular alpha-synuclein (ASN) could be involved in the pathomechanism of Parkinson's disease (PD) via disturbances of calcium homeostasis, activation of nitric oxide synthase and oxidative/nitrosative stress. In this study we analyzed the role of cyclin-dependent kinase 5 (Cdk5) in the molecular mechanism(s) of ASN toxicity. We found that exposure of PC12 cells to ASN increases Cdk5 activity via calpain-dependent p25 formation and by enhancement of Cdk5 phosphorylation at Tyr15. Cdk5 and calpain inhibitors prevented ASN-evoked cell death. Our findings, indicating the participation of Cdk5 in ASN toxicity, provide new insight into how extracellular ASN may trigger dopaminergic cell dysfunction in PD. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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