Nutritional, Genetic, and Molecular Aspects of Manganese Intoxication

Manganese (Mn) is an essential heavy metal and a neurotoxicant. Daily intake through dietary sources provides the necessary amount of Mn required for several physiological processes, including antioxidant defense, energy metabolism, immune function, and bone development. Nevertheless, excessive exposure to Mn is toxic and may arise from environmental sources, occupational exposure, total parenteral nutrition, or methcathinone drug abuse. Several proteins have been identified to transport Mn, such as divalent metal tranporter-1, SLC30A10 (solute carrier family 30, member 10), transferrin, and ferroportin, to name a few. Accumulation of Mn occurs mainly in basal ganglia and leads to a syndrome called manganism. The molecular mechanisms of Mn neurotoxicity include oxidative stress, mitochondrial impairment, and neurotransmitter dyshomeostasis leading to cognitive dysfunction and motor symptoms similar to Parkinson's disease (PD). Given the similarities between manganism and PD, understanding nutritional and molecular aspects of Mn transport and toxicity may help to understand the mechanisms underlying the etiology of PD and possibly other neurodegenerative disorders.