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

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.

Research Highlights
► Manganese induced the overexpression of α-synuclein though an ERK1/2M APK dependent manner.
► Both the inhibition of ERK1/2 MAPK and the knockdown of α-synuclein alleviated manganese-induced cytotoxicity.
► These findings suggest that manganese induces toxicity through an ERK1/2 MAPK/α-synuclein-dependent pathway.