Zeitschrift für Arzneimittelstoffwechsel und Toxikologie
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Mechanisms of Heavy Metal Neurotoxicity: Lead and Manganese

April P. Neal and Tomás R. Guilarte

Human exposure to heavy metals is a global public health problem. Heavy metals which cause neurological toxicity, such as lead (Pb2+) and manganese (Mn), are of particular concern due to the long-lasting and possibly irreversible nature of their effects. Pb2+ exposure in childhood can result in cognitive and behavioral deficits in children. These effects are long-lasting and persist into adulthood even after Pb2+ exposure has been reduced or eliminated. While Mn is an essential element of the human diet and serves many cellular functions in the human body, elevated Mn levels can result in a Parkinson’s disease (PD)-like syndrome and developmental Mn exposure can adversely affect childhood neurological development. Due to the ubiquitous presence of both metals, reducing human exposure to toxic levels of Mn and Pb2+ remains a world-wide public health challenge. In this review we summarize the toxicokinetics of Pb2+ and Mn, describe their neurotoxic mechanisms, and discuss common themes in heavy metal toxicology.