Manganese-induced oxidative stress

Some regions of the brain, especially the basal ganglia, are particularly susceptible to excess manganese, and excessive accumulation there may result in the neurodegenerative disorder manganism. Research efforts into the poorly understood molecular mechanisms by which elevated manganese levels in the brain could cause neuronal dysfunction and death have increased. The most popular model suggests that excess manganese causes imbalance of the mitochondrial redox activity, which may then lead to proliferation of cellular oxidative stress (OS). Such a mitochondrial event may be a key step in the demise of the affected central nervous system (CNS) cells. This chapter discusses the sources, absorption, and transportation of manganese, as well as the nature of manganese toxicities reported in humans. The chapter also addresses the mechanistic hypothesis that manganese induces OS in areas of the brain where it accumulates most, thereby leading to the onset of neurotoxicity.