title: The neurotoxicity of iron, copper and manganese in Parkinson's and Wilson's diseases.
abstract: Impaired cellular homeostasis of metals, particularly of Cu, Fe and Mn may trigger neurodegeneration through various mechanisms, notably induction of oxidative stress, promotion of α-synuclein aggregation and fibril formation, activation of microglial cells leading to inflammation and impaired production of metalloproteins. In this article we review available studies concerning Fe, Cu and Mn in Parkinson's disease and Wilson's disease. In Parkinson's disease local dysregulation of iron metabolism in the substantia nigra (SN) seems to be related to neurodegeneration with an increase in SN iron concentration, accompanied by decreased SN Cu and ceruloplasmin concentrations and increased free Cu concentrations and decreased ferroxidase activity in the cerebrospinal fluid. Available data in Wilson's disease suggest that substantial increases in CNS Cu concentrations persist for a long time during chelating treatment and that local accumulation of Fe in certain brain nuclei may occur during the course of the disease. Consequences for chelating treatment strategies are discussed.
authors: Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, 1st Faculty of Medicine and General University Hospital in Prague, Czech Republic; Institute of Neuroradiology, University Medicine Göttingen, Göttingen, Germany. Electronic address: pdusek@gmail.com.
authors: Petr
authors: P
authors: Dusek
authors: Department of Neurology, Division of Clinical Neurophysiology, Oslo University Hospital, Oslo, Norway; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors: Per M
authors: PM
authors: Roos
authors: 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland.
authors: Tomasz
authors: T
authors: Litwin
authors: Neurology Department, University of Kiel, Kiel, Germany.
authors: Susanne A
authors: SA
authors: Schneider
authors: Department of Chemistry, Norwegian University of Science and Technology, Trondheim, Norway.
authors: Trond Peder
authors: TP
authors: Flaten
authors: Department of Medicine, Innlandet Hospital Trust, Kongsvinger Hospital Division, Kongsvinger, Norway.
authors: Jan
authors: J
authors: Aaseth
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D003300:Copper / Q000378:metabolism* / Q000633:toxicity; D004195:Disease Models, Animal; D004781:Environmental Exposure / Q000009:adverse effects; D006527:Hepatolenticular Degeneration / Q000378:metabolism* / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000633:toxicity; D008345:Manganese / Q000378:metabolism* / Q000633:toxicity; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D008345:Manganese; D003300:Copper; D007501:Iron
keywords: Chelating agents; Copper; Iron; Manganese; Parkinson's disease; Wilson's disease