The relevance of iron in the pathogenesis of Parkinson's disease.
Investigations that revealed increased levels of iron in postmortem brains from patients with Parkinson's disease (PD) as compared to those from individuals not suffering from neurological disorders are reported. The chemical natures in which iron predominates in the brain and the relevance of neuromelanin for neuronal iron binding are discussed. Major findings have been that iron levels increase with the severity of neuropathological changes in PD, presumably due to increased transport through the blood-brain barrier in late stages of parkinsonism. Glial iron is mainly stored as ferric iron in ferritin, while neuronal iron is predominantly bound to neuromelanin. Iron overload may induce progressive degeneration of nigrostriatal neurons by facilitating the formation of reactive biological intermediates, including reactive oxygen species, and the formation of cytotoxic protein aggregates. There are indications that iron-mediated neuronal death in PD proceeds retrogradely. These results are also discussed with respect to their relevance for disease progression in relation to cytotoxic alpha-synuclein protofibril formation.
Götz
Mario E
ME
Department of Pharmacology and Toxicology, University of Würzburg, Germany. mgoetz@pharmakologie.uni-kiel.de
Double
Kay
K
Gerlach
Manfred
M
Youdim
Moussa B H
MB
Riederer
Peter
P
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008543:Melanins / Q000378:metabolism; D008959:Models, Neurological; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D020734:Parkinsonian Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D008543:Melanins; C014121:neuromelanin; D005293:Ferritins; D007501:Iron; D004298:Dopamine