The nervous system is a susceptible target for a variety of toxic metals. Metal-induced neurotoxicity is described in humans in connection with environmental pollution (lead, methylmercury), occupational exposure (elemental mercury, lead, manganese), use of medicinal agents (lithium, cisplatin, bismuth, gold salts), and accidental ingestion of pesticides and rodenticides containing arsenic or thallium salts. Neurobiology of metals has received widespread scientific attention, and several monographs dealing with this topic have already been published. This chapter summarizes the metals and metallic compounds that can be classified as genuine neurotoxicants because of their documented etiological role in human disease. The induction of a particular response is usually related to the absorbed dose and the presence of a critical metal concentration at the target site in the nervous system. Chronic exposure to certain neurotoxic metals is implicated in the pathophysiology of certain neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Nervous system disease can also be induced by metal deficiency. Zinc, copper, and manganese are examples of beneficial trace elements whose deficiency may lead to neurological disorders. Aging is generally associated with an increased risk for some forms of neurotoxicity, an observation that stems in part from reduced hepatic and renal circulation, decreased biotransformation capacity, and diminished renal and biliary excretion of xenobiotics.
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