Oxidative basis of manganese neurotoxicity

Exposure to excessive levels of manganese, an essential trace element, can evoke severe psychiatric and extrapyramidal motor dysfunction closely resembling Parkinson's disease. The clinical manifestations of manganese toxicity arise from focal injury to the basal ganglia. This region, characterized by intense consumption of oxygen and significant dopamine content, can incur mitochondrial dysfunction, depletion of levels of peroxidase and catalase, and catecholamine biochemical imbalances following manganese exposure. The site specificity of the pathology and the nature of the cellular damage caused by manganese have been attributed to its capacity to produce cytotoxic levels of free radicals. However, support for such a pro-oxidant role for manganese has been largely limited to inferences drawn from histopathological observations. More recently, research efforts into the molecular details of manganese toxicity have provided evidence of an etiological relationship between oxidative stress and manganese-related neurodegeneration. This review focuses on studies that evaluate the redox chemistry of manganese during the neurodegenerative process and its molecular consequences.