Anamorsin attenuates cupric chloride-induced dopaminergic neuronal cell death.

Neurodegenerative diseases are associated with elevated levels of metal elements, which are well-known inducers of reactive oxygen species (ROS) in cells. Because dopaminergic neurons in the substantia nigra are vulnerable to ROS, dysregulation of metals and the resulting accumulation of ROS could be a cause of dopaminergic neurodegeneration. In this study, we showed that overexpression of anamorsin protected MN9D dopaminergic neuronal cells from cupric chloride-induced death. This cytoprotection was achieved by specifically decreasing ROS levels. As determined by mini two-dimensional electrophoretic assay, an acidic shift of anamorsin occurred during drug-induced death, which seemed to be mediated by oxidative modification of three of its CXXC motifs. Consequently, drug-induced dissociation of ASK1 from Trx1 and subsequent phosphorylation of JNK and p38 MAPK were inhibited in MN9D cells overexpressing anamorsin. Taken together, our results indicate that anamorsin exerts a neuroprotective effect by reducing intracellular ROS levels and subsequently attenuating activated stress-activated MAP kinases pathways.