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Brain Res. 2010 Nov 4;1359:201-7. doi: 10.1016/j.brainres.2010.08.055. Epub 2010 Aug 22.

Manganese induces the overexpression of α-synuclein in PC12 cells via ERK activation.

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Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.


Manganese has been known to induce neurological disorders. In the present study, we determined the effect of manganese on the expression of α-synuclein in PC12 cells and its role in manganese-induced cytotoxicity. We also investigated the relationship between α-synuclein expression and the change of ERK1/2 MAPK activity. In our research, manganese exposure induced the overexpression of α-synuclein, while siRNA knockdown of α-synuclein reversed manganese-induced cytotoxicity. Furthermore, manganese induced the activation of ERK1/2 MAPK. The MEK1 inhibitor PD98059, which inhibits the activation of ERK MAPK, attenuated the overexpression of α-synuclein and the cytotoxicity induced by manganese. In conclusion, our studies show that manganese may induce the overexpression of α-synuclein via ERK1/2 activation, which may play a role in manganese-induced cytotoxicity.

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