VanDuyn, NataliaNass, Richard2016-03-182016-03-182014-03VanDuyn, N., & Nass, R. (2014). The putative multidrug resistance protein MRP-7 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans. Journal of Neurochemistry, 128(6), 962–974. http://doi.org/10.1111/jnc.12515https://hdl.handle.net/1805/8931Parkinson’s disease (PD) is the most prevalent neurodegenerative motor disorder worldwide, and results in the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta. Gene-environment interactions are believed to play a significant role in the vast majority of PD cases, yet the toxicants and the associated genes involved in the neuropathology are largely ill-defined. Recent epidemiological and biochemical evidence suggests that methylmercury (MeHg) may be an environmental toxicant that contributes to the development of PD. Here we report that a gene coding for the putative multidrug resistance protein MRP-7 in Caenorhabditis elegans (C. elegans) modulates whole animal and DA neuron sensitivity to MeHg. In this study we demonstrate that genetic knockdown of MRP-7 results in a 2-fold increase in Hg levels and a dramatic increase in stress response proteins associated with the endoplasmic reticulum, golgi apparatus, and mitochondria, as well as an increase in MeHg-associated animal death. Chronic exposure to low concentrations of MeHg induces MRP-7 gene expression, while exposures in MRP-7 genetic knockdown animals results in a loss of DA neuron integrity without affecting whole animal viability. Furthermore, transgenic animals expressing a fluorescent reporter behind the endogenous MRP-7 promoter indicate that the transporter is expressed in DA neurons. These studies show for the first time that a multidrug resistance protein is expressed in DA neurons, and its expression inhibits MeHg-associated DA neuron pathology.en-USPublisher PolicyneurodegenerationneurotoxicityParkinson’s diseasemethylmercuryArticle