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Development of manganism (also known as manganese neurotoxicity) is a major complication of manganese exposure in which neurological dysfunction is linked to accumulation of the metal in brain. Due to neuronal cell death in basal ganglia structures, particularly the globus pallidus, functional recovery is limited. Bearing a resemblance to Parkinson's disease, effective treatment for manganism is currently limited. However, the rapidly developing field of stem cell research offers new hope for the treatment of illnesses in which neurodegeneration is a major feature. The first part of this review will focus on the clinical features and pathophysiology of cerebral damage resulting from exposure to manganese, including the role of astrocytes, disruption of energy metabolism, involvement of oxidative stress, excitotoxicity, and inflammation, with the second part exploring how stem cells may provide an important therapeutic strategy for patients with this major neurologic disorder.Manganism is associated with cerebral accumulation of manganese and neuronal loss in basal ganglia structures.Uptake of manganese by astrocytes represents a major feature of the disorder.Energy impairment due to mitochondrial sequestering of manganese leads to development of oxidative stress, excitotoxicity and inflammation.Stem cell treatment represents a major potential therapeutic strategy for treating these damaging processes in manganism.