title: Neurodegenerative diseases and therapeutic strategies using iron chelators.
abstract: This review will summarise the current state of our knowledge concerning the involvement of iron in various neurological diseases and the potential of therapy with iron chelators to retard the progression of the disease. We first discuss briefly the role of metal ions in brain function before outlining the way by which transition metal ions, such as iron and copper, can initiate neurodegeneration through the generation of reactive oxygen and nitrogen species. This results in protein misfolding, amyloid production and formation of insoluble protein aggregates which are contained within inclusion bodies. This will activate microglia leading to neuroinflammation. Neuroinflammation plays an important role in the progression of the neurodegenerative diseases, with activated microglia releasing pro-inflammatory cytokines leading to cellular cell loss. The evidence for metal involvement in Parkinson's and Alzheimer's disease as well as Friedreich's ataxia and multiple sclerosis will be presented. Preliminary results from trials of iron chelation therapy in these neurodegenerative diseases will be reviewed.
authors.affiliation: Centre for Neuroinflammation & Neurodegeneration, Imperial College London, Hammersmith Hospital Campus, London W120NN, UK; Universite Catholique de Louvain, Louvain-la-Neuve, Belgium. Electronic address: roberta.ward@uclouvain.be.
authors.forename: Roberta J
authors.initials: RJ
authors.lastname: Ward
authors.affiliation: Centre for Neuroinflammation & Neurodegeneration, Imperial College London, Hammersmith Hospital Campus, London W120NN, UK.
authors.forename: David T
authors.initials: DT
authors.lastname: Dexter
authors.affiliation: Universite Catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Crichton
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005621:Friedreich Ataxia / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism*; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism
chemical_list: D007502:Iron Chelating Agents; D007501:Iron
keywords: Chelation; Iron; Neurodegenerative diseases