Intracellular signal transduction pathways as targets for neurotoxicants.
The multiple cascades of signal transduction pathways that lead from receptors on the cell membrane to the nucleus, thus translating extracellular signals into changes in gene expression, may represent important targets for neurotoxic compounds. Among the biochemical steps and pathways that have been investigated are the metabolism of cyclic nucleotides, the formation of nitric oxide, the metabolism of membrane phospholipids, the activation of a multitude of protein kinases and the induction of transcription factors. This brief review will focus on the interactions of three known neurotoxicants, lead, ethanol and polychlorinated biphenyls, with signal transduction pathways, particularly the family of protein kinase C isozymes, and discusses how such effects may be involved in their neurotoxicity.
Department of Environmental Health, University of Washington, 4225 Roosevelt #100, Seattle, WA 98105, USA. lgcosta@u.washington.edu
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Costa
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Guizzetti
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H
Lu
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Bordi
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Vitalone
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Tita
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Palmery
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Valeri
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Silvestrini
D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes; D007854:Lead / Q000633:toxicity*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D007527:Isoenzymes; D009498:Neurotoxins; D007854:Lead; D000431:Ethanol; D011078:Polychlorinated Biphenyls; D011493:Protein Kinase C