Journal
ANNUAL REVIEW OF NUTRITION, VOL 35
Volume 35, Issue -, Pages 71-108Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-nutr-071714-034419
Keywords
neurodevelopment; cofactor; blood-brain barrier; metal transport; homeostasis; intracellular trafficking
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Funding
- National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) [R01 ES10563, R01 ES16931]
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES016931, R01ES010563, T32ES007028] Funding Source: NIH RePORTER
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The understanding of manganese (Mn) biology, in particular its cellular regulation and role in neurological disease, is an area of expanding interest. Mn is an essential micronutrient that is required for the activity of a diverse set of enzymatic proteins (e.g., arginase and glutamine synthase). Although necessary for life, Mn is toxic in excess. Thus, maintaining appropriate levels of intracellular Mn is critical. Unlike other essential metals, cell-level homeo-static mechanisms of Mn have not been identified. In this review, we discuss common forms of Mn exposure, absorption, and transport via regulated uptake/exchange at the gut and blood-brain barrier and via biliary excretion. We present the current understanding of cellular uptake and efflux as well as subcellular storage and transport of Mn. In addition, we highlight the Mn-dependent and Mn-responsive pathways implicated in the growing evidence of its role in Parkinson's disease and Huntington's disease. We conclude with suggestions for future focuses of Mn health-related research.
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