Impact of environmental toxicants on p38- and ERK-MAPK signaling pathways in the central nervous system.

There are several candidate signalling pathways that mediate the response of the central nervous system (CNS) cells to environmental toxins. However, much is still to be learned on how these pathways modulate neurotoxicity. The mitogen-activated protein kinases (MAPKs) signalling pathways, which include the extracellular signal-regulated protein kinase (ERK) and the p38-MAPK, are potentially key pathways to regulate CNS responses to environmental toxins. The pathways play leading roles in the transmission of extracellular signals into the cell nucleus, leading to cell differentiation, cell growth, and apoptosis, to name a few. Moreover, exposure to environmental toxins induces p38- and ERK-MAPK activation, which leads to oxidative stress, inflammation, and apoptosis in the CNS. Here, we provide a concise review of the recent evidence demonstrating the role of p38- and ERK-MAPK signaling pathways and their downstream targets in the CNS following exposure to environmental toxicants such as metals, organophosphorus and persistent organic pollutants.