title: Manganese Is Essential for Neuronal Health.
abstract: 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 homeostatic 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.
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, Tennessee 37232; email: kyle.j.horning@vanderbilt.edu , k.grace.tipps@vanderbilt.edu , aaron.bowman@vanderbilt.edu.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Horning
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Caito
authors.forename: K Grace
authors.initials: KG
authors.lastname: Tipps
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Bowman
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
mesh_terms: D001119:Arginase / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006304:Health Status; D006706:Homeostasis; D006801:Humans; D006816:Huntington Disease; D007408:Intestinal Absorption; D008345:Manganese / Q000494:pharmacology / Q000502:physiology* / Q000633:toxicity; D009422:Nervous System Diseases; D009474:Neurons / Q000502:physiology*; D010300:Parkinson Disease
chemical_list: D008345:Manganese; D001119:Arginase; D005974:Glutamate-Ammonia Ligase
keywords: blood-brain barrier; cofactor; homeostasis; intracellular trafficking; metal transport; neurodevelopment