Abstract：
:α-Synuclein (α-syn) and oxidative stress play pivotal roles in the pathogenesis of Parkinson's disease (PD). However, the mechanisms underlying the interaction between α-syn and oxidative stress remain poorly understood. The present study provides evidence to suggest that the nuclear translocation of α-syn increases death of dopaminergic neurons in response to oxidative stress. We found that administration of H2O2 induced a rapid cleavage and nuclear translocation of α-syn in cultured MES23.5 cells. Inhibition of calpain proteolysis, using a calpain inhibitor (MDL-28170), significantly blocked cleavage and nuclear translocation of α-syn and attenuated H2O2-induced cell death in MES23.5 cells. Expression of a truncated fragment of α-syn (58-140) significantly increased the cell death induced by H2O2 treatment. These results suggest that calpain proteolysis is involved in the process of nuclear translocation of α-syn in MES23.5 dopaminergic cells induced by oxidative stress, and that nuclear translocation of α-syn increases susceptibility of these cells to oxidative stress. Taken together, our findings provide new insight into the interaction between α-syn and oxidative stress through activation of calpain proteolytic activity.
journal_name
Brain Resjournal_title
Brain researchauthors
Zhou M,Xu S,Mi J,Uéda K,Chan Pdoi
10.1016/j.brainres.2013.01.024subject
Has Abstractpub_date
2013-03-15 00:00:00pages
19-27eissn
0006-8993issn
1872-6240pii
S0006-8993(13)00077-2journal_volume
1500pub_type
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