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Theme 11 ALS Pathogenesis and Neurotoxicity

Background: Manganese (Mn) is a trace element vital for human health as it serves as a cofactor for many enzymes critical for development, metabolism and redox homeostasis. However, excessive exposure to Mn results in a severe neurological disorder referred to as ‘‘manganism’’. Its clinical expression is classically described to mainly resemble Parkinson’s disease, but at lower levels, chronic Mn overexposure has more subtle effects on cognitive and motor abilities, some reminiscent of ALS, such as muscle weakness. Mn smelters and miners have been described to develop both ALS and manganism in different parts of the world. Mn overload was also suggested to be implicated in the high incidence of the ALS-Parkinson’s Dementia Complex in Guam and the Kii Peninsula. Finally, increased Mn levels were measured in diverse bodily fluids and in the spinal cord of ALS patients and animal models.