Journal of Organic & Inorganic Chemistry

Manganese-induced neurotoxicity: lessons from worms to human neonates

Annual Congress on Medicinal Chemistry, Pharmacology and toxicology
July 30 - 31 , 2018 Amsterdam , Netherlands

Michael Aschner

Albert Einstein College of Medicine, New York, USA

Posters & Accepted Abstracts: J Org Inorg Chem

DOI: 10.21767/2472-1123-C3-009

Abstract

Manganese (Mn) is a trace metal required for normal physiological processes in humans. Mn levels are tightly regulated, as high levels of Mn results 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. Homozygous mutations in SLC30A10 cause familial Parkinsonism associated with manganese (Mn) retention. We recently identified SLC30A10 to be a cell surface-localized Mn efflux transporter and demonstrated that Parkinsonism causing mutations block its intracellular trafficking and efflux function. In C. elegans, SLC30A10 over-expression protected against Mn-induced lethality and dopaminergic neurotoxicity, consistent with results in mammalian systems. SLC30A10 expression did not protect worms against ZnSO4 toxicity, suggesting that SLC30A10 does not mediate Zn export in C. elegans.