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J Neural Transm (Vienna). 2011 Aug;118(8):1165-72. doi: 10.1007/s00702-011-0596-7. Epub 2011 Feb 20.

α-Synuclein increases U251 cells vulnerability to hydrogen peroxide by disrupting calcium homeostasis.

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  • 1School of Life Science, Beijing Institute of Technology, No. 5 Zhongguancun Nandajie, Haidian District, Beijing, 100081, People's Republic of China.


Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by glial cytoplasmic inclusions containing insoluble α-synuclein. Since Ca(2+) plays an important role in cell degeneration, [Ca(2+)]( i ) in α-synuclein-overexpressed human glioma cells was analyzed by Fura-2 fluorometry. Overexpression of α-synuclein increased the basal level of [Ca(2+)]( i ), and a higher Ca(2+) response to hydrogen peroxide was further observed. The effect that α-synuclein overexpression caused U251 cells to be more vulnerable to hydrogen peroxide was eliminated by Ca(2+) chelator BAPTA-AM or transient receptor potential channels blocker SKF 96365 but not by L-type Ca(2+) channel blocker nimodipine. These findings suggest that the dysregulation of cellular Ca(2+) homeostasis caused by α-synuclein under oxidative stress may contribute to the glial cell death in MSA.

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