title: From manganism to manganese-induced parkinsonism: a conceptual model based on the evolution of exposure.
abstract: Manganism is a distinct medical condition from Parkinson's disease. Manganese exposure scenarios in the last century generally have changed from the acute, high-level exposure conditions responsible for the occurrence of manganism to chronic exposure to much lower levels. Such chronic exposures may progressively extend the site of manganese deposition and toxicity from the globus pallidus to the entire area of the basal ganglia, including the substantia nigra pars compacta involved in Parkinson's disease. The mechanisms of manganese neurotoxicity from chronic exposure to very low levels are not well understood, but promising information is based on the concept of susceptibility that may place individuals exposed to manganese at a higher risk for developing Parkinsonian disturbances. These conditions include mutations of genes which play important pathogenetic roles in both Parkinsonism and in the regulation of manganese transport and metabolism. Liver function is also important in manganese-related neurotoxicity and sub-clinical impairment may increase the risk of Parkinsonism. The purpose and scope of this report are to explore the literature concerning manganese exposure and potential subclinical effects and biological pathways, impairment, and development of diseases such as Parkinsonism and manganism. Inhalation and ingestion of manganese will be the focus of this report.
authors.affiliation: Department of Experimental and Applied Medicine, Section of Occupational Health and Industrial Hygiene, University of Brescia, Brescia, Italy.
authors.forename: Roberto G
authors.initials: RG
authors.lastname: Lucchini
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Martin
authors.forename: Brent C
authors.initials: BC
authors.lastname: Doney
mesh_terms: D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D004781:Environmental Exposure; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008345:Manganese / Q000378:metabolism / Q000633:toxicity*; D020149:Manganese Poisoning / Q000150:complications* / Q000378:metabolism*; D016273:Occupational Exposure; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000473:pathology; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D014896:Welding; D000078329:Workforce; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
chemical_list: C514983:ATP13A2 protein, human; D051844:alpha-Synuclein; D008345:Manganese; D044767:Ubiquitin-Protein Ligases; D006180:Proton-Translocating ATPases