Advanced search
Publication Cover
Future Neurology Volume 3, 2008 - Issue 4
Submit an article Journal homepage
41
Views
0
CrossRef citations to date
0
Altmetric
Review

Contribution of Disturbed Iron Metabolism to the Pathogenesis of Parkinson‘s Disease

Daniela Berga Center of Neurology, Department of Neurodegeneration & Hertie Institute for Clinical Brain Research, 72076 Tübingen, Germany. Tel: +49 7071 298 3119; Fax: +49 7071 29 4608; [email protected]Correspondence[email protected]
,
Peter Riedererb University of Würzburg, Department of Psychiatry & Psychotherapy and, National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases Research, Laboratory for Clinical Neurochemistry, Würzburg, Germany. Tel: +49 931 201 77200; Fax: +49 931 201 77220; [email protected]
&
Manfred Gerlachc University of Würzburg, Department of Child & Adolescent Psychiatry & Psychotherapy, Laboratory for Clinical Neurobiology, Würzburg, Germany. Tel: +49 931 201 78020; Fax: +49 931 201 77680; [email protected]
Pages 447-461 | Published online: 12 Jun 2008

Bibliography

  • Tan EK : The role of common genetic risk variants in Parkinson disease.Clin. Genet.72(5), 387–393 (2007).
  • Edwards TM , MyersJP: Environmental exposures and gene regulation in disease etiology.Environ. Health Perspect.115(9), 1264–1270 (2007).
  • Elbaz A , TranchantC: Epidemiologic studies of environmental exposures in Parkinson‘s disease.J. Neurol. Sci.262(1–2), 37–44 (2007).
  • Elbaz A , DufouilC, AlperovitchA: Interaction between genes and environment in neurodegenerative diseases.C R Biol.330(4), 318–328 (2007).
  • Riederer P , RauschWD, SchmidtBet al.: Biochemical fundamentals of Parkinson‘s disease. Mt Sinai J. Med.55(1), 21–28 (1988).
  • Riederer P , SoficE, RauschWDet al.: Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J. Neurochem.52(2), 515–520 (1989).
  • Sofic E , RiedererP, HeinsenHet al.: Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J. Neural Transm.74(3), 199–205 (1988).
  • Sofic E , PaulusW, JellingerK, RiedererP, YoudimMB: Selective increase of iron in substantia nigra zona compacta of parkinsonian brains.J. Neurochem.56(3), 978–982 (1991).
  • Gerlach M , Ben-ShacharD, RiedererP, YoudimMB: Altered brain metabolism of iron as a cause of neurodegenerative diseases?J. Neurochem.63(3), 793–807 (1994).
  • Berg D , GerlachM, YoudimMBet al.: Brain iron pathways and their relevance to Parkinson‘s disease. J. Neurochem.79(2), 225–236 (2001).
  • Gotz ME , DoubleK, GerlachM, Youdim MB, Riederer P: The relevance of iron in the pathogenesis of Parkinson‘s disease. Ann. NY Acad. Sci.1012, 193–208 (2004).
  • Gerlach M , DoubleKL, YoudimMB, RiedererP: Potential sources of increased iron in the substantia nigra of parkinsonian patients.J. Neural Transm. Suppl.70, 133–142 (2006).
  • Morawski M , MeineckeC, ReinertTet al.: Determination of trace elements in the human substantia nigra. Nucl. Instrum. Methods Phys. Res. B.231, 224–228 (2005).
  • Oakley AE , CollingwoodJF, DobsonJet al.: Individual dopaminergic neurons show raised iron levels in Parkinson disease. Neurology68(21), 1820–1825 (2007).
  • Jellinger K , PaulusW, Grundke-IqbalI, RiedererP, YoudimMB: Brain iron and ferritin in Parkinson‘s and Alzheimer‘s diseases.J. Neural Transm. Park. Dis. Dement. Sect.2(4), 327–340 (1990).
  • Jellinger K , KienzlE, RumpelmairGet al.: Iron–melanin complex in substantia nigra of parkinsonian brains: an x-ray microanalysis. J. Neurochem.59(3), 1168–1171 (1992).
  • Yoshida T , TanakaM, SotomatsuA, HiraiS, OkamotoK: Activated microglia cause iron-dependent lipid peroxidation in the presence of ferritin.Neuroreport9(9), 1929–1933 (1998).
  • Schipper HM , VininskyR, BrullR, SmallL, BrawerJR: Astrocyte mitochondria: a substrate for iron deposition in the aging rat substantia nigra.Exp. Neurol.152(2), 188–196 (1998).
  • Warmuth-Metz M , NaumannM, CsotiI, SolymosiL: Measurement of the midbrain diameter on routine magnetic resonance imaging: a simple and accurate method of differentiating between Parkinson disease and progressive supranuclear palsy.Arch. Neurol.58(7), 1076–1079 (2001).
  • Schenck JF : Magnetic resonance imaging of brain iron.J. Neurol. Sci.207(1–2), 99–102 (2003).
  • Drayer BP , OlanowW, BurgerP, Johnson GA, Herfkens R, Riederer S: Parkinson plus syndrome: diagnosis using high field MR imaging of brain iron. Radiology159(2), 493–498 (1986).
  • Norfray JF , ChiaradonnaNL, HeiserWJet al.: Brain iron in patients with Parkinson disease: MR visualization using gradient modification. Am. J. Neuroradiol.9(2), 237–240 (1988).
  • Brooks DJ , LuthertP, GadianD, Marsden CD: Does signal-attenuation on high-field T2-weighted MRI of the brain reflect regional cerebral iron deposition? Observations on the relationship between regional cerebral water proton T2 values and iron levels. J. Neurol. Neurosurg. Psychiatr.52(1), 108–111 (1989).
  • Bartzokis G , CummingsJL, MarkhamCHet al.: MRI evaluation of brain iron in earlier- and later-onset Parkinson‘s disease and normal subjects. Magn. Reson. Imaging17(2), 213–222 (1999).
  • Antonini A , LeendersKL, MeierD, Oertel WH, Boesiger P, Anliker M: T2 relaxation time in patients with Parkinson‘s disease. Neurology43(4), 697–700 (1993).
  • Atasoy HT , NuyanO, TuncT, Yorubulut M, Unal AE, Inan LE: T2-weighted MRI in Parkinson‘s disease; substantia nigra pars compacta hypointensity correlates with the clinical scores. Neurol. India52(3), 332–337 (2004).
  • Ordidge RJ , GorellJM, DeniauJC, Knight RA, Helpern JA: Assessment of relative brain iron concentrations using T2-weighted and T2*-weighted MRI at 3 Tesla. Magn. Reson. Med.32(3), 335–341 (1994).
  • Gorell JM , OrdidgeRJ, BrownGG, Deniau JC, Buderer NM, Helpern JA: Increased iron-related MRI contrast in the substantia nigra in Parkinson‘s disease. Neurology45(6), 1138–1143 (1995).
  • Oikawa H , SasakiM, TamakawaY, EharaS, TohyamaK: The substantia nigra in Parkinson disease: proton density-weighted spin-echo and fast short inversion time inversion-recovery MR findings.Am. J. Neuroradiol.23(10), 1747–1756 (2002).
  • Hutchinson M , RaffU, LebedevS: MRI correlates of pathology in parkinsonism: segmented inversion recovery ratio imaging (SIRRIM).Neuroimage20(3), 1899–1902 (2003).
  • Graham JM , PaleyMN, GrunewaldRA, HoggardN, GriffithsPD: Brain iron deposition in Parkinson‘s disease imaged using the PRIME magnetic resonance sequence.Brain123(Pt 12), 2423–2431 (2000).
  • Michaeli S , OzG, SorceDJet al.: Assessment of brain iron and neuronal integrity in patients with Parkinson‘s disease using novel MRI contrasts. Mov. Disord.22(3), 334–340 (2007).
  • Bartzokis G , CummingsJ, PerlmanS, HanceDB, MintzJ: Increased basal ganglia iron levels in Huntington disease.Arch. Neurol.56(5), 569–574 (1999).
  • Haacke EM , AyazM, KhanAet al.: Establishing a baseline phase behavior in magnetic resonance imaging to determine normal vs abnormal iron content in the brain. J. Magn. Reson. Imaging26(2), 256–264 (2007).
  • Brass SD , ChenNK, MulkernRV, Bakshi R: Magnetic resonance imaging of iron deposition in neurological disorders. Top. Magn. Reson. Imaging17(1), 31–40 (2006).
  • Kosta P , ArgyropoulouMI, MarkoulaS, KonitsiotisS: MRI evaluation of the basal ganglia size and iron content in patients with Parkinson‘s disease.J. Neurol.253(1), 26–32 (2006).
  • Stankiewicz J , PanterSS, NeemaM, Arora A, Batt CE, Bakshi R: Iron in chronic brain disorders: imaging and neurotherapeutic implications. Neurotherapeutics4(3), 371–386 (2007).
  • Berg D , SiefkerC, BeckerG: Echogenicity of the substantia nigra in Parkinson‘s disease and its relation to clinical findings.J. Neurol.248(8), 684–689 (2001).
  • Walter U , WittstockM, BeneckeR, Dressler D: Substantia nigra echogenicity is normal in non-extrapyramidal cerebral disorders but increased in Parkinson‘s disease. J. Neural Transm.109(2), 191–196 (2002).
  • Becker G , SeufertJ, BogdahnU, ReichmannH, ReinersK: Degeneration of substantia nigra in chronic Parkinson‘s disease visualized by transcranial color-coded real-time sonography.Neurology45(1), 182–184 (1995).
  • Spiegel J , HellwigD, MollersMOet al.: Transcranial sonography and 123IFP-CIT SPECT disclose complementary aspects of Parkinson‘s disease. Brain129(Pt 5), 1188–1193 (2006).
  • Ressner P , SkoloudikD, HlustikP, Kanovsky P: Hyperechogenicity of the substantia nigra in Parkinson‘s disease. J. Neuroimaging17(2), 164–167 (2007).
  • Okawa M , MiwaH, KajimotoYet al.: Transcranial sonography of the substantia nigra in Japanese patients with Parkinson‘s disease or atypical parkinsonism: clinical potential and limitations. Intern. Med.46(18), 1527–1531 (2007).
  • Huang YW , JengJS, TsaiCF, ChenLL, Wu RM: Transcranial imaging of substantia nigra hyperechogenicity in a Taiwanese cohort of Parkinson‘s disease. Mov. Disord.22(4), 550–555 (2007).
  • Tsai CF , WuRM, HuangYW, ChenLL, Yip PK, Jeng JS: Transcranial color-coded sonography helps differentiation between idiopathic Parkinson‘s disease and vascular parkinsonism. J. Neurol.254(4), 501–507 (2007).
  • Gaenslen A , UnmuthB, GodauJ, LiepeltI, Di Santo A, Schweitzer KJ: Prospective evaluation of the specificity and sensitivity of transcranial ultrasound in the differential diagnosis of Parkinson‘s disease. Lancet Neurol. (2008) (In Press).
  • Berg D , GroteC, RauschWDet al.: Iron accumulation in the substantia nigra in rats visualized by ultrasound. Ultrasound Med. Biol.25(6), 901–904 (1999).
  • Berg D , BeckerG, ZeilerBet al.: Vulnerability of the nigrostriatal system as detected by transcranial ultrasound. Neurology53(5), 1026–1031 (1999).
  • Berg D , RoggendorfW, SchroderUet al.: Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch. Neurol.59(6), 999–1005 (2002).
  • Zecca L , BergD, ArzbergerTet al.: In vivo detection of iron and neuromelanin by transcranial sonography: a new approach for early detection of substantia nigra damage. Mov. Disord.20(10), 1278–1285 (2005).
  • Berg D , SiefkerC, Ruprecht-DorflerP, BeckerG: Relationship of substantia nigra echogenicity and motor function in elderly subjects.Neurology56(1), 13–17 (2001).
  • Berg D , JabsB, MerschdorfU, Beckmann H, Becker G: Echogenicity of substantia nigra determined by transcranial ultrasound correlates with severity of parkinsonian symptoms induced by neuroleptic therapy. Biol. Psychiatry50(6), 463–467 (2001).
  • Thomas M , HayflickSJ, JankovicJ: Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden–Spatz syndrome) and pantothenate kinase-associated neurodegeneration.Mov. Disord.19(1), 36–42 (2004).
  • Kaur D , YantiriF, RajagopalanSet al.: Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson‘s disease. Neuron37(6), 899–909 (2003).
  • Ruprecht-Dorfler P , BergD, TuchaOet al.: Echogenicity of the substantia nigra in relatives of patients with sporadic Parkinson‘s disease. Neuroimage18(2), 416–422 (2003).
  • Felletschin B , BauerP, WalterUet al.: Screening for mutations of the ferritin light and heavy genes in Parkinson‘s disease patients with hyperechogenicity of the substantia nigra. Neurosci. Lett.352(1), 53–56 (2003).
  • Deplazes J , SchobelK, HochstrasserHet al.: Screening for mutations of the IRP2 gene in Parkinson‘s disease patients with hyperechogenicity of the substantia nigra. J. Neural Transm.111(4), 515–521 (2004).
  • Hochstrasser H , BauerP, WalterUet al.: Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease. Neurology63(10), 1912–1917 (2004).
  • Akbas N , HochstrasserH, DeplazesJet al.: Screening for mutations of the HFE gene in Parkinson‘s disease patients with hyperechogenicity of the substantia nigra. Neurosci. Lett.407(1), 16–19 (2006).
  • Berg D , HochstrasserH, SchweitzerKJ, RiessO: Disturbance of iron metabolism in Parkinson‘s disease – ultrasonography as a biomarker.Neurotox. Res.9(1), 1–13 (2006).
  • Klomp LW , GitlinJD: Expression of the ceruloplasmin gene in the human retina and brain: implications for a pathogenic model in aceruloplasminemia.Hum. Mol. Genet.5(12), 1989–1996 (1996).
  • Curtis AR , FeyC, MorrisCMet al.: Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat. Genet.28(4), 350–354 (2001).
  • Kohno S , MiyajimaH, TakahashiY, Inoue Y: Aceruloplasminemia with a novel mutation associated with parkinsonism. Neurogenetics2(4), 237–238 (2000).
  • Bosio S , De Gobbi M, Roetto Aet al.: Anemia and iron overload due to compound heterozygosity for novel ceruloplasmin mutations. Blood100(6), 2246–2248 (2002).
  • Thompson K , MenziesS, MuckenthalerMet al.: Mouse brains deficient in H-ferritin have normal iron concentration but a protein profile of iron deficiency and increased evidence of oxidative stress. J. Neurosci. Res.71(1), 46–63 (2003).
  • LaVaute T , SmithS, CoopermanSet al.: Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat. Genet.27(2), 209–214 (2001).
  • Borie C , GaspariniF, VerpillatPet al.: Association study between iron-related genes polymorphisms and Parkinson‘s disease. J. Neurol.249(7), 801–804 (2002).
  • Costa-Mallen P , CheckowayH, ZabetiAet al.: The functional polymorphism of the hemoglobin-binding protein haptoglobin influences susceptibility to idiopathic Parkinson‘s disease. Am. J. Med. Genet. B. Neuropsychiatr. Genet.147B(2), 216–222 (2007).
  • Haaxma CA , BloemBR, BormGFet al.: Gender differences in Parkinson‘s disease. J. Neurol. Neurosurg. Psychiatr.78(8), 819–824 (2007).
  • Bartzokis G , TishlerTA, LuPHet al.: Brain ferritin iron may influence age- and gender-related risks of neurodegeneration. Neurobiol. Aging28(3), 414–423 (2007).
  • Xu X , WangQ, ZhangM: Age, gender, and hemispheric differences in iron deposition in the human brain: an in vivo MRI study.Neuroimage40(1), 35–42 (2008).
  • Oestreicher E , SengstockGJ, RiedererP, OlanowCW, DunnAJ, ArendashGW: Degeneration of nigrostriatal dopaminergic neurons increases iron within the substantia nigra: a histochemical and neurochemical study.Brain Res.660(1), 8–18 (1994).
  • Kortekaas R , LeendersKL, van Oostrom JCet al.: Blood–brain barrier dysfunction in parkinsonian midbrain in vivo.Ann. Neurol.57(2), 176–179 (2005).
  • Tanner CM , OttmanR, GoldmanSMet al.: Parkinson disease in twins: an etiologic study. JAMA281(4), 341–346 (1999).
  • Lan J , JiangDH: Excessive iron accumulation in the brain: a possible potential risk of neurodegeneration in Parkinson‘s disease.J. Neural Transm.104(6–7), 649–660 (1997).
  • Kaur D , PengJ, ChintaSJet al.: Increased murine neonatal iron intake results in Parkinson-like neurodegeneration with age. Neurobiol. Aging28(6), 907–913 (2007).
  • Peng IF , BerkeBA, ZhuY, LeeWH, Chen W, Wu CF: Temperature-dependent developmental plasticity of Drosophila neurons: cell-autonomous roles of membrane excitability, Ca2+ influx, and cAMP signaling. J. Neurosci.27(46), 12611–12622 (2007).
  • Dick FD , De Palma G, Ahmadi Aet al.: Environmental risk factors for Parkinson‘s disease and parkinsonism: the Geoparkinson study. Occup. Environ. Med.64(10), 666–672 (2007).
  • Dick FD , De Palma G, Ahmadi Aet al.: Gene–environment interactions in parkinsonism and Parkinson‘s disease: the Geoparkinson study. Occup. Environ. Med.64(10), 673–680 (2007).
  • Faucheux BA , NillesseN, DamierPet al.: Expression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson disease. Proc. Natl Acad. Sci. USA92(21), 9603–9607 (1995).
  • Faucheux BA , HauwJJ, AgidY, HirschEC: The density of 125I-transferrin binding sites on perikarya of melanized neurons of the substantia nigra is decreased in Parkinson‘s disease.Brain Res.749(1), 170–174 (1997).
  • Morris CM , CandyJM, OmarS, Bloxham CA, Edwardson JA: Transferrin receptors in the parkinsonian midbrain. Neuropathol. Appl. Neurobiol.20(5), 468–472 (1994).
  • Dexter DT , CarayonA, VidailhetMet al.: Decreased ferritin levels in brain in Parkinson‘s disease. J. Neurochem.55(1), 16–20 (1990).
  • Logroscino G , MarderK, GrazianoJet al.: Dietary iron, animal fats, and risk of Parkinson‘s disease. Mov. Disord.13(Suppl. 1), 13–16 (1998).
  • Torsdottir G , KristinssonJ, SveinbjornsdottirS, SnaedalJ, Johannesson T: Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson‘s disease. Pharmacol. Toxicol.85(5), 239–243 (1999).
  • Leveugle B , FaucheuxBA, BourasCet al.: Cellular distribution of the iron-binding protein lactotransferrin in the mesencephalon of Parkinson‘s disease cases. Acta Neuropathol.91(6), 566–572 (1996).
  • Hallgren B , SouranderP: The effect of age on the non-haem iron in the human brain.J. Neurochem.3(1), 41–51 (1958).
  • Dwork AJ , LawlerG, ZybertPAet al.: An autoradiographic study of the uptake and distribution of iron by the brain of the young rat. Brain Res.518(1–2), 31–39 (1990).
  • Mann VM , CooperJM, DanielSEet al.: Complex I, iron, and ferritin in Parkinson‘s disease substantia nigra. Ann. Neurol.36(6), 876–881 (1994).
  • Connor JR , SnyderBS, BeardJL, FineRE, MufsonEJ: Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer‘s disease.J. Neurosci. Res.31(2), 327–335 (1992).
  • Connor JR , SnyderBS, ArosioP, Loeffler DA, LeWitt P: A quantitative analysis of isoferritins in select regions of aged, parkinsonian, and Alzheimer‘s diseased brains. J. Neurochem.65(2), 717–724 (1995).
  • Griffiths PD , DobsonBR, JonesGR, ClarkeDT: Iron in the basal ganglia in Parkinson‘s disease. An in vitro study using extended x-ray absorption fine structure and cryo-electron microscopy.Brain122(Pt 4), 667–673 (1999).
  • Meneghini R : Iron homeostasis, oxidative stress, and DNA damage.Free Radic. Biol. Med.23(5), 783–792 (1997).
  • Hu J , ConnorJR: Demonstration and characterization of the iron regulatory protein in human brain.J. Neurochem.67(2), 838–844 (1996).
  • Smith MA , WehrK, HarrisPL, SiedlakSL, ConnorJR, PerryG: Abnormal localization of iron regulatory protein in Alzheimer‘s disease.Brain Res.788(1–2), 232–236 (1998).
  • Boyer RF , GrabillTW, PetrovichRM: Reductive release of ferritin iron: a kinetic assay.Anal. Biochem.174(1), 17–22 (1988).
  • Monteiro HP , WinterbournCC: 6-hydroxydopamine releases iron from ferritin and promotes ferritin-dependent lipid peroxidation.Biochem. Pharmacol.38(23), 4177–4182 (1989).
  • Lapenna D , DegioiaS, CiofaniG, CuccurulloF: Captopril induces iron release from ferritin and oxidative stress.J. Pharm. Pharmacol.47, 59–61 (1995).
  • Double KL , MaywaldM, SchmittelM, RiedererP, GerlachM: In vitro studies of ferritin iron release and neurotoxicity.J. Neurochem.70(6), 2492–2499 (1998).
  • Biemond P , van Eijk HG, Swaak AJ, Koster JF: Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes. Possible mechanism in inflammation diseases. J. Clin. Invest.73(6), 1576–1579 (1984).
  • Reif DW , SimmonsRD: Nitric oxide mediates iron release from ferritin.Arch. Biochem. Biophys.283(2), 537–541 (1990).
  • Youdim MB , Ben-ShacharD, RiedererP: The possible role of iron in the etiopathology of Parkinson‘s disease.Mov. Disord.8(1), 1–12 (1993).
  • Yoshida T , TanakaM, SotomatsuA, Hirai S: Activated microglia cause superoxide-mediated release of iron from ferritin. Neurosci. Lett.190(1), 21–24 (1995).
  • Napolitano A , CrescenziO, PezzellaA, ProtaG: Generation of the neurotoxin 6-hydroxydopamine by peroxidase/H2O2 oxidation of dopamine.J. Med. Chem.38(6), 917–922 (1995).
  • Jellinger K , LinertL, KienzlE, Herlinger E, Youdim MB: Chemical evidence for 6-hydroxydopamine to be an endogenous toxic factor in the pathogenesis of Parkinson‘s disease. J. Neural Transm. Suppl.46, 297–314 (1995).
  • Linert W , HerlingerE, JamesonRF, Kienzl E, Jellinger K, Youdim MB: Dopamine, 6-hydroxydopamine, iron, and dioxygen – their mutual interactions and possible implication in the development of Parkinson‘s disease. Biochim. Biophys. Acta1316(3), 160–168 (1996).
  • Andrew R , WatsonDG, BestSA, Midgley JM, Wenlong H, Petty RK: The determination of hydroxydopamines and other trace amines in the urine of parkinsonian patients and normal controls. Neurochem. Res.18(11), 1175–1177 (1993).
  • Connor JR , MenziesSL, St Martin SM, Mufson EJ: Cellular distribution of transferrin, ferritin, and iron in normal and aged human brains. J. Neurosci. Res.27(4), 595–611 (1990).
  • Double KL , GerlachM, YoudimMB, RiedererP: Impaired iron homeostasis in Parkinson‘s disease.J. Neural Transm. Suppl.60, 37–58 (2000).
  • Fedorow H , PickfordR, HookJMet al.: Dolichol is the major lipid component of human substantia nigra neuromelanin. J. Neurochem.92(4), 990–995 (2005).
  • Lopiano L , DigilioG, FasanoMet al.: Iron and neuromelanin in Parkinson‘s disease. J. Neural Transm.106, 24 (1999).
  • Gerlach M , TrautweinAX, ZeccaL, Youdim MB, Riederer P: Mossbauer spectroscopic studies of purified human neuromelanin isolated from the substantia nigra. J. Neurochem.65(2), 923–926 (1995).
  • Double KL , GerlachM, SchunemannVet al.: Iron-binding characteristics of neuromelanin of the human substantia nigra. Biochem. Pharmacol.66(3), 489–494 (2003).
  • Good PF , OlanowCW, PerlDP: Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson‘s disease: a LAMMA study.Brain Res.593(2), 343–346 (1992).
  • Zecca L , ShimaT, StroppoloAet al.: Interaction of neuromelanin and iron in substantia nigra and other areas of human brain. Neuroscience73(2), 407–415 (1996).
  • Kienzl E , PuchingerL, JellingerK, Linert W, Stachelberger H, Jameson RF: The role of transition metals in the pathogenesis of Parkinson‘s disease. J. Neurol. Sci.134(Suppl.) 69–78 (1995).
  • Double KL , RiedererP, GerlachM: Significance of neuromelanin for neurodegeneration in Parkinson‘s disease.Drug News Perspect.12, 333–340 (1999).
  • Schipper HM : Heme oxygenase expression in human central nervous system disorders.Free Radic. Biol. Med.37(12), 1995–2011 (2004).
  • Polymeropoulos MH , LavedanC, LeroyEet al.: Mutation in the α-synuclein gene identified in families with Parkinson‘s disease. Science276(5321), 2045–2047 (1997).
  • Kruger R , KuhnW, MullerTet al.: Ala30Pro mutation in the gene encoding α-synuclein in Parkinson‘s disease. Nat. Genet.18(2), 106–108 (1998).
  • Singleton AB , FarrerM, JohnsonJet al.: α-synuclein locus triplication causes Parkinson‘s disease. Science302(5646), 841 (2003).
  • Golts N , SnyderH, FrasierM, TheislerC, ChoiP, WolozinB: Magnesium inhibits spontaneous and iron-induced aggregation of α-synuclein.J. Biol. Chem.277(18), 16116–16123 (2002).
  • Hashimoto M , RockensteinE, CrewsL, MasliahE: Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer‘s and Parkinson‘s diseases.Neuromolecular Med.4(1–2), 21–36 (2003).
  • Giasson BI , DudaJE, MurrayIVet al.: Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science290(5493), 985–989 (2000).
  • Munch G , LuthHJ, WongAet al.: Crosslinking of α-synuclein by advanced glycation endproducts – an early pathophysiological step in Lewy body formation?J. Chem. Neuroanat.20(3–4), 253–257 (2000).
  • Lee EN , LeeSY, LeeD, KimJ, PaikSR: Lipid interaction of α-synuclein during the metal-catalyzed oxidation in the presence of Cu2+ and H2O2.J. Neurochem.84(5), 1128–1142 (2003).
  • Bharathi , IndiSS, RaoKS: Copper- and iron-induced differential fibril formation in α-synuclein: TEM study.Neurosci. Lett.424(2), 78–82 (2007).
  • Uversky VN : Neuropathology, biochemistry, and biophysics of α-synuclein aggregation.J. Neurochem.103(1), 17–37 (2007).
  • Cole NB , MurphyDD, LebowitzJ, Di NotoL, LevineRL, NussbaumRL: Metal-catalyzed oxidation of α-synuclein: helping to define the relationship between oligomers, protofibrils, and filaments.J. Biol. Chem.280(10), 9678–9690 (2005).
  • Jenner P , OlanowCW: Understanding cell death in Parkinson‘s disease.Ann. Neurol.44(3 Suppl. 1), S72–S84 (1998).
  • Gaeta A , HiderRC: The crucial role of metal ions in neurodegeneration: the basis for a promising therapeutic strategy.Br. J. Pharmacol.146(8), 1041–1059 (2005).
  • Castellani RJ , SiedlakSL, PerryG, Smith MA: Sequestration of iron by Lewy bodies in Parkinson‘s disease. Acta Neuropathol. (Berl.)100(2), 111–114 (2000).
  • Turnbull S , TabnerBJ, El-AgnafOM, Moore S, Davies Y, Allsop D: α-synuclein implicated in Parkinson‘s disease catalyses the formation of hydrogen peroxide in vitro. Free Radic. Biol. Med.30(10), 1163–1170 (2001).
  • Junn E , MouradianMM: Human α-synuclein over-expression increases intracellular reactive oxygen species levels and susceptibility to dopamine.Neurosci. Lett.320(3), 146–150 (2002).
  • Wang C , KoHS, ThomasBet al.: Stress-induced alterations in parkin solubility promote parkin aggregation and compromise parkin‘s protective function. Hum. Mol. Genet.14(24), 3885–3897 (2005).
  • Jimenez Del Rio M , MorenoS, Garcia-OspinaGet al.: Autosomal recessive juvenile parkinsonism Cys212Tyr mutation in parkin renders lymphocytes susceptible to dopamine- and iron-mediated apoptosis. Mov. Disord.19(3), 324–330 (2004).
  • Yao D , GuZ, NakamuraTet al.: Nitrosative stress linked to sporadic Parkinson‘s disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity. Proc. Natl Acad. Sci. USA101(29), 10810–10814 (2004).
  • Lipton SA , NakamuraT, YaoD, ShiZQ, UeharaT, GuZ: Comment on ‘S-nitrosylation of parkin regulates ubiquitination and compromises parkin‘s protective function‘.Science308(5730), 1870; author reply 1870 (2005).
  • Pawlyk AC , GiassonBI, SampathuDMet al.: Novel monoclonal antibodies demonstrate biochemical variation of brain parkin with age. J. Biol. Chem.278(48), 48120–48128 (2003).
  • Nishikawa K , LiH, KawamuraRet al.: Alterations of structure and hydrolase activity of parkinsonism-associated human ubiquitin carboxyl-terminal hydrolase L1 variants. Biochem. Biophys. Res. Commun.304(1), 176–183 (2003).
  • Choi J , LeveyAI, WeintraubSTet al.: Oxidative modifications and down-regulation of ubiquitin carboxyl-terminal hydrolase L1 associated with idiopathic Parkinson‘s and Alzheimer‘s diseases. J. Biol. Chem.279(13), 13256–13264 (2004).
  • Chung KK , ThomasB, LiXet al.: S-nitrosylation of parkin regulates ubiquitination and compromises parkin‘s protective function. Science304(5675), 1328–1331 (2004).
  • Ciechanover A , BrundinP: The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg.Neuron40(2), 427–446 (2003).
  • Zhou W , ZhuM, WilsonMA, PetskoGA, FinkAL: The oxidation state of DJ-1 regulates its chaperone activity toward α-synuclein.J. Mol. Biol.356(4), 1036–1048 (2006).
  • Shendelman S , JonasonA, MartinatC, LeeteT, AbeliovichA: DJ-1 is a redox-dependent molecular chaperone that inhibits α-synuclein aggregate formation.PLoS Biol.2(11), E362 (2004).
  • Mizuno Y , OhtaS, TanakaMet al.: Deficiencies in complex I subunits of the respiratory chain in Parkinson‘s disease. Biochem. Biophys. Res. Commun.163(3), 1450–1455 (1989).
  • Reichmann H , JanetzkyB: Mitochondrial dysfunction – a pathogenetic factor in Parkinson‘s disease.J. Neurol.247(Suppl. 2), II63–II68 (2000).
  • Beal MF : Mitochondrial dysfunction and oxidative damage in Alzheimer‘s and Parkinson‘s diseases and coenzyme Q10 as a potential treatment.J. Bioenerg. Biomembr.36(4), 381–386 (2004).
  • Liu Y , FiskumG, SchubertD: Generation of reactive oxygen species by the mitochondrial electron transport chain.J. Neurochem.80(5), 780–787 (2002).
  • Liu B , GaoHM, WangJY, JeohnGH, CooperCL, HongJS: Role of nitric oxide in inflammation-mediated neurodegeneration.Ann. NY Acad. Sci.962, 318–331 (2002).
  • Shamoto-Nagai M , MaruyamaW, KatoYet al.: An inhibitor of mitochondrial complex I, rotenone, inactivates proteasome by oxidative modification and induces aggregation of oxidized proteins in SH–SY5Y cells. J. Neurosci. Res.74(4), 589–597 (2003).
  • Kotake Y , OhtaS: MPP+ analogs acting on mitochondria and inducing neuro-degeneration.Curr. Med. Chem.10(23), 2507–2516 (2003).
  • Gu M , CooperJM, TaanmanJW, Schapira AH: Mitochondrial DNA transmission of the mitochondrial defect in Parkinson‘s disease. Ann. Neurol.44(2), 177–186 (1998).
  • Carreras MC , FrancoMC, PeraltaJG, PoderosoJJ: Nitric oxide, complex I, and the modulation of mitochondrial reactive species in biology and disease.Mol. Aspects Med.25(1–2), 125–139 (2004).
  • Naoi M , MaruyamaW, AkaoY, ZhangJ, ParvezH: Apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, in dopamine neurons.Toxicology153(1–3), 123–141 (2000).
  • Davis GC , WilliamsAC, MarkeySPet al.: Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiatry Res.1(3), 249–254 (1979).
  • Langston JW , BallardP, TetrudJW, IrwinI: Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis.Science219(4587), 979–980 (1983).
  • Chan TS , TengS, WilsonJX, GalatiG, Khan S, O‘Brien PJ: Coenzyme Q cytoprotective mechanisms for mitochondrial complex I cytopathies involves NAD(P)H: quinone oxidoreductase 1(NQO1). Free Radic. Res.36(4), 421–427 (2002).
  • Sherer TB , BetarbetR, StoutAKet al.: An in vitro model of Parkinson‘s disease: linking mitochondrial impairment to altered α-synuclein metabolism and oxidative damage. J. Neurosci.22(16), 7006–7015 (2002).
  • Fiskum G , StarkovA, PolsterBM, ChinopoulosC: Mitochondrial mechanisms of neural cell death and neuroprotective interventions in Parkinson‘s disease.Ann. NY Acad. Sci.991, 111–119 (2003).
  • Kanthasamy AG , KitazawaM, KaulSet al.: Proteolytic activation of proapoptotic kinase PKCδ is regulated by overexpression of Bcl-2: implications for oxidative stress and environmental factors in Parkinson‘s disease. Ann. NY Acad. Sci.1010, 683–686 (2003).
  • Rossi L , LombardoMF, CirioloMR, Rotilio G: Mitochondrial dysfunction in neurodegenerative diseases associated with copper imbalance. Neurochem. Res.29(3), 493–504 (2004).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.