Manganese-induced neurotoxicity: from C. elegans to humans

Abstract

Manganese (Mn) is one of the most abundant metals on the earth. It is required for normal cellular activities, but overexposure leads to toxicity. Neurons are more susceptible to Mn-induced toxicity than other cells, and accumulation of Mn in the brain results in Manganism that presents with Parkinson's disease (PD)-like symptoms. In the last decade, a number of Mn transporters have been identified, which improves our understanding of Mn transport in and out of cells. However, the mechanism of Mn-induced neurotoxicity is only partially uncovered, with further research needed to explore the whole picture of Mn-induced toxicity. In this review, we will address recent progress in Mn-induced neurotoxicity from C. elegans to humans, and explore future directions that will help understand the mechanisms of its neurotoxicity.

Hepatic metal ion transporter ZIP8 regulates manganese homeostasis and manganese-dependent enzyme activity

“…Patients carrying SLC39A8 mutations had neurological and skeletal abnormalities that were evident very early in life (16-18). ZIP8-iKO and ZIP8-LSKO mice did not exhibit such abnormalities, been shown to cause manganism characterized by neurological and behavioral disorders resembling Parkinson's disease (27,41). Our discovery that ZIP8 maintains whole-body Mn homeostasis by scavenging Mn from biliary excretion suggests that SLC39A8 may be a therapeutic target for inhibition in the treatment of Mn intoxication and provides a rationale for Mn supplementation as a treatment of patients with SLC39A8 mutations leading to CDG (SLC39A8-CDG).…”

Assessing human metal accumulations in an urban superfund site

“…Manganese is an essential trace micro-nutrient that plays an essential role in various physiological processes (Chen, P. et al, 2015). There are well documented toxic effects from excess Mn exposure, which was first described in 1897 by James Couper and described as a neurological disease (“manganism”) (Luccihini et al, 2009).…”

SLC30A10: A novel manganese transporter

“…It is required for many enzymatic activities (such as superoxide dismutase, arginase and pyruvate carboxylase) across different species. 1 Mn is abundant in the food chain and environment. It is available from whole grains, legumes, rice and nuts, as well as chocolate, tea, leafy green vegetables and some fruits like blueberries, but at smaller amounts.…”