Metals
and Neurotoxicology
Metals are ubiquitous and play a critical
role in neurobiology. Transition metals are important because they alter the
redox state of the physical environment. Biologically, transition metals
catalyze redox reactions that are critical to cellular res-piration, chemical
detoxification, metabolism, and even neurotransmitter synthesis. Many metals
are both nutrients and neurotoxicants, such as iron, zinc, copper, and
manganese. Other metals, such as lead and cadmium, are metabolized similarly to
these metals, particularly iron. Iron metabolism and genes that regulate iron
metabolism may be the key to understanding metal toxicity. Finally, recent
evidence demonstrates that early life exposures may program later life and
adult disease phenotypes via processes of epigenetics. Parallel work in metals
demonstrates that epigenetics may be a critical pathway by which metals produce
health effects. J. Nutr. 137: 2809–2813, 2007.
The biological effects of metals are linked
to their chemical prop-erties. Transition metals (such as Cu, Fe, and Mn) are
particularly adept at catalyzing redox reactions within biological systems. Zn
is a nutrient metal that in high dosage can paradoxically promote oxidative
toxicity. Heavy metals (Pb, Cd) and metal-loids (As) can also induce oxidative
toxicity but more likely work by binding to proteins and interfering with metal
transport and protein function. Although Pb and methylmercury neuro-toxicity is
well established, the effects of other metals on brain development have only
recently drawn attention. Unfortunately, it appears that excess metal exposure
may be a common source. of neurotoxicity in multiple populations around the
world. Although metals have multiple effects on biological systems, an
understudied effect is their role in programming gene ex-pression. A growing
body of evidence suggests that metals may influence epigenetic phenomena which
regulate the expression of genes and ultimately their protein products. In this
article, we focus on the neurotoxic properties of metals and their ability to
mimic the pathways of Fe metabolism. In addition, we review the data on the
effects of metals on DNA methylation and discuss how these properties might
explain fetal origins of adult disease.
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