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S11-2 Manganese-induced neurotoxicity: lessons from worms
  1. Michael Aschner
  1. Albert Einstein College of Medicine, Bronx, USA

Abstract

Manganese (Mn), is a trace metal required for normal physiological processes in humans. Mn levels are tightly regulated, as high levels of Mn result in accumulation in the brain and cause a neurological disease known as manganism. Manganism shares many similarities with Parkinson’s disease (PD), both at the physiological level and the cellular level. Exposure to high Mn-containing environments increases the risk of developing manganism. Combining genetics and biochemical assays, we established in the nematode (C. elegans) and other experimental models that dopamine (DA) is responsible for Mn-induced DAergic neurodegeneration, and that this process (1) requires functional DA-reuptake transporter (DAT-1), (2) is associated with oxidative stress and lifespan reduction, (3) and is enhanced by iron deficiency. The presentation will focus on the mechanisms of Mn uptake and efflux into the brain, genetic susceptibility to Mn-induced damage, and molecular mechanisms of neurotoxicity. (This research was supported by a grant from the National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) R01 ES10563).

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