While the increase in life expectancy globally is a welcome trend, increases in age-related neurodegenerative disease will be one of the fastest growing sources of disability and societal burden. Growing evidence generated from cell, animal, and epidemiological studies supports the etiological role of environmental agents, such as pesticides [e.g., paraquat (PQ)] and metals [e.g., manganese (Mn)] in parkinsonian syndromes, a group of age-related neurodegenerative diseases. Human translational studies, however, are challenged by the long latency between exposure and clinical diagnosis, lack of practical tools to ascertain prior neurotoxicant exposure and biomarkers to gauge neurodegenerative pathological processes. The proposed seed grant is based on the novel premise that exposure to pesticides (e.g., PQ) and to welding fumes (e.g., Mn) will trigger unique patterns of metabolites and miRNA expression that will allow identification of specific mechanisms (e.g., inflammation, excitotoxicity, oxidative stress) that are critical in leading to neurotoxicity in individuals exposed to pesticides and/or welding fumes.
