Journal
NEUROBIOLOGY OF AGING
Volume 33, Issue 12, Pages 2841-2854Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2012.02.001
Keywords
SNCA; Mitochondrial dynamic; DLP1; ERK
Categories
Funding
- National Program of Basic Research of China [2007CB947900, 2010CB945200, 2011CB504104]
- Natural Science Fund [30700888, 30770732, 30872729, 30971031, 30870879, 81071024, 81171202]
- Key Discipline Program of Shanghai Municipality [S30202]
- Shanghai Key Project of Basic Science Research [10411954500]
- Shanghai Pujiang Program [09PJ1407500]
- Program for Outstanding Medical Academic Leader of Shanghai [LJ 06003]
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Compounding evidence suggests that alpha-synuclein (SNCA) plays an important role in the pathogenesis of Parkinson's disease (PD) by inducing neurotoxicity. Mitochondria are highly dynamic organelles that undergo fusion and fission processes, the imbalance of which has been viewed as a key trigger for PD. However, the underlying relationship between SNCA and mitochondrial dynamics remains unclear. This study demonstrated that SNCA overexpression not only altered mitochondrial morphology, but also significantly increased the translocation of mitochondrial fission protein dynamin-like protein 1 (DLP1). To further investigate the mechanism of SNCA's effect on mitochondrial dynamics, the proteomic technique, stable isotope labeling of amino acid in cell cultures (SILAC), was used. The extracellular signal-regulated kinase (ERK) was confirmed to be involved in the regulation of DLP1 and SNCA-mediated neurotoxicity. Finally, additional results demonstrated that SNCA inducing both mitochondrial dynamic disorders and neurotoxicity could be ameliorated by curcumin through ERK inhibition, which implied that the agent could be used to prevent and treat PD in the future. (C) 2012 Elsevier Inc. All rights reserved.
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