Emerging neurotoxic mechanisms in environmental factors-induced neurodegeneration.

Exposure to environmental neurotoxic metals, pesticides and other chemicals is increasingly recognized as a key risk factor in the pathogenesis of chronic neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Oxidative stress and apoptosis have been actively investigated as neurotoxic mechanisms over the past two decades, resulting in a greater understanding of neurotoxic processes. Nevertheless, emerging evidence indicates that epigenetic changes, protein aggregation and autophagy are important cellular and molecular correlates of neurodegenerative diseases resulting from chronic neurotoxic chemical exposure. During the Joint Conference of the 13th International Neurotoxicology Association and the 11th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health, the recent progress made toward understanding epigenetic mechanisms, protein aggregation, autophagy, and deregulated kinase activation following neurotoxic chemical exposure and the relevance to neurodegenerative conditions were one of the themes of the symposium. Dr. Anumantha G. Kanthasamy described the role of acetylation of histones and non-histone proteins in neurotoxicant-induced neurodegenerative processes in the nigral dopaminergic neuronal system. Dr. Arthi Kanthasamy illustrated the role of autophagy as a key determinant in cell death events during neurotoxic insults. Dr. Ajay Rana provided evidence for posttranslational modification of α-synuclein protein by the Mixed Linage Kinase (MLK) group of kinases to initiate protein aggregation in cell culture and animal models of Parkinson's disease. These presentations outlined emerging cutting edge mechanisms that might set the stage for future mechanistic investigations into new frontiers of molecular neurotoxicology. This report summarizes the views of symposium participants, with emphasis on future directions for study of environmentally and occupationally linked chronic neurodegenerative diseases.