Manganese neurotoxicity: A bioinorganic chemist’s perspective

Manganese is an essential metal for life, yet chronic exposure to this metal can cause a neurodegenerative disease named manganism, with symptoms that resemble Parkinson’s disease. Mn accumulates in the striatum and damages this brain structure that controls motor function; however, the molecular mechanisms underlying this neurodegenerative disease are poorly understood. In this short review, a summary of the current knowledge on the mechanisms involved in Mn neurotoxicity is given, with a special emphasis on the features that suggest specific protein–manganese interactions. The mechanisms of Mn uptake into the brain are discussed, displaying its similarities to Fe metabolism. Cellular trafficking of Mn is also reviewed, pointing out at its connection to Ca homeostasis, and its relevance for understanding Mn-induced neuronal death. The main purpose of this review is to provide a glimpse of an unexplored bioinorganic facet of a Mn-induced neurodegenerative disease.

Graphical abstractManganism is a Mn-induced neurodegenerative disease. This short review is a summary of the mechanisms involved in Mn neurotoxicity, with emphasis on potential protein–manganese interactions. The connections of Mn uptake and homeostasis with Fe metabolism and Ca homeostasis are highlighted. This article provides a glimpse of an unexplored bioinorganic facet of manganism.Figure optionsDownload full-size imageDownload as PowerPoint slide