title: Manganese homeostasis in the nervous system.
abstract: Manganese (Mn) is an essential heavy metal that is naturally found in the environment. Daily intake through dietary sources provides the necessary amount required for several key physiological processes, including antioxidant defense, energy metabolism, immune function and others. However, overexposure from environmental sources can result in a condition known as manganism that features symptomatology similar to Parkinson's disease (PD). This disorder presents with debilitating motor and cognitive deficits that arise from a neurodegenerative process. In order to maintain a balance between its essentiality and neurotoxicity, several mechanisms exist to properly buffer cellular Mn levels. These include transporters involved in Mn uptake, and newly discovered Mn efflux mechanisms. This review will focus on current studies related to mechanisms underlying Mn import and export, primarily the Mn transporters, and their function and roles in Mn-induced neurotoxicity. Though and essential metal, overexposure to manganese may result in neurodegenerative disease analogous to Parkinson's disease. Manganese homeostasis is tightly regulated by transporters, including transmembrane importers (divalent metal transporter 1, transferrin and its receptor, zinc transporters ZIP8 and Zip14, dopamine transporter, calcium channels, choline transporters and citrate transporters) and exporters (ferroportin and SLC30A10), as well as the intracellular trafficking proteins (SPCA1 and ATP12A2). A manganese-specific sensor, GPP130, has been identified, which affords means for monitoring intracellular levels of this metal.
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Pan
authors.initials: P
authors.lastname: Chen
authors.affiliation: Neuroscience Graduate Program, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Division of Pharmacology & Toxicology, College of Pharmacy; Institute for Cellular & Molecular Biology; and Institute for Neuroscience, The University of Texas at Austin, Austin, Texas, USA.
authors.forename: Somshuvra
authors.initials: S
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Physiology, Meharry Medical College, Nashville, Tennessee, USA.
authors.forename: Eunsook
authors.initials: E
authors.lastname: Lee
authors.affiliation: Graduate Program in Public Health, Department of Pathology, Clinical and Toxicological Analysis, Center of Health Science, State University of Londrina, Parana, Brazil.
authors.forename: Monica M B
authors.initials: MM
authors.lastname: Paoliello
authors.affiliation: Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Bowman
authors.affiliation: Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA.|Neuroscience Graduate Program, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
mesh_terms: D000818:Animals; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008345:Manganese / Q000378:metabolism* / Q000633:toxicity; D020149:Manganese Poisoning / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000378:metabolism; D010300:Parkinson Disease / Q000175:diagnosis / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology
chemical_list: D026901:Membrane Transport Proteins; D008345:Manganese
keywords: Parkinson's disease; manganese; transport