Intracellular signal transduction pathways as targets for neurotoxicants

The multiple cascades of signal transduction pathways that lead from recept ors on the cell membrane to the nucleus, thus translating extracellular sig nals into changes in gene expression, may represent important targets for n eurotoxic compounds. Among the biochemical steps and pathways that have bee n investigated are the metabolism of cyclic nucleotides, the formation of n itric oxide, the metabolism of membrane phospholipids, the activation of a multitude of protein kinases and the induction of transcription factors. Th is brief review will focus on the interactions of three known neurotoxicant s, lead, ethanol and polychlorinated biphenyls, with signal transduction pa thways, particularly the family of protein kinase C isozymes, and discusses how such effects may be involved in their neurotoxicity. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.