Manganese neurotoxicity: A bioinorganic chemist’s perspective |
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Authors: | Liliana Quintanar [Author Vitae] |
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Affiliation: | Departamento de Química, Centro de Investigación y de Estudios Avanzados (Cinvestav), Av. IPN No. 2508, Col. San Pedro Zacatenco, Deleg, Gustavo A. Madero, México 07360, D.F., Mexico |
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Abstract: | 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. |
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Keywords: | ACDP, ancient conserved domain protein (the name of a family of proteins) ATP, adenosine triphosphate BBB, blood-brain barrier DA, dopamine DAT, dopamine transporter DMT-1, divalent metal transporter 1 (also known as Nramp2) DNA, deoxyribonucleic acid EGTA, ethylene glycol-bis(β-aminoethylether)-N,N,N&prime ,N&prime -tetraacetic acid EPR, electron paramagnetic resonance ER, endoplasmic reticulum GABA, mmlsi6" onclick=" submitCitation('/science?_ob=MathURL& _method=retrieve& _eid=1-s2.0-S0020169307005464& _mathId=si6.gif& _pii=S0020169307005464& _issn=00201693& _acct=C000051805& _version=1& _userid=1154080& md5=a1a47fad3b99597ea37f785e72cf8873')" style=" cursor:pointer " alt=" Click to view the MathML source" title=" Click to view the MathML source" > formulatext" title=" click to view the MathML source" >γ-aminobutyric acid GLAST, glutamate:aspartate transporter Gln, glutamine Glu, glutamate GluR, glutamate receptor hCp, human ceruloplasmin Mam3p, the name of a vacuole membrane protein (member of the ACDP family) MMT, methylcyclopentadienyl-manganese-tricarbonyl MnSOD, manganese superoxide dismutase MTM1, name of a manganese trafficking factor for mitochondrial SOD Nramp, natural-resistance-associated macrophage protein (a family of metal ion transporters) PC12, pheochromocytoma (a type of cell) Pho84p, name of a manganese transporter in yeast Pmr1p, name of a P-type ATPase (yeast homologue of SPCA) SERCA, sarcoendoplasmic reticulum calcium ATPase SMF1, name of a yeast homologue of DMT-1 SOD, superoxide dismutase SPCA, secretory pathway calcium ATPase 2 (human homologue of Pmr1p) Stases, sugar transferases Tf, transferrin TfR, transferrin receptor XANES, X-ray absorption near-edge spectroscopy |
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