Nigral iron elevation is an invariable feature of Parkinson's disease and is a sufficient cause of neurodegeneration

BioMed Research International

Volumn 2014, Issue , 2014, Pages

  Ayton, Scott ^a   Lei, Peng ^a  

^a UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

IRON;

ADOLESCENT; ADULT; CHEMISTRY; CHILD; CYTOLOGY; HUMAN; METABOLISM; MIDDLE AGED; NERVE CELL; PARKINSON DISEASE; PATHOPHYSIOLOGY; REVIEW; SUBSTANTIA NIGRA; YOUNG ADULT;

ADOLESCENT; ADULT; CHILD; HUMANS; IRON; MIDDLE AGED; NEURONS; PARKINSON DISEASE; SUBSTANTIA NIGRA; YOUNG ADULT;

EID: 84893774898     PISSN: 23146133     EISSN: 23146141     Source Type: Journal    
DOI: 10.1155/2014/581256     Document Type: Review

References (134)

1. Braak H., Rüb U., Gai W. P., Del Tredici K., Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. Journal of Neural Transmission 2003 110 5 517 536 2-s2.0-0038748401 10.1007/s00702-002-0808-2 (Pubitemid 36543283)
2. Götz M. E., Double K., Gerlach M., Youdim M. B. H., Riederer P., The relevance of iron in the pathogenesis of Parkinson's disease. Annals of the New York Academy of Sciences 2004 1012 193 208 2-s2.0-11144353557 10.1196/annals.1306.017 (Pubitemid 38455479)
3. Zecca L., Gallorini M., Schünemann V., Trautwein A. X., Gerlach M., Riederer P., Vezzoni P., Tampellini D., Iron, neuromelanin and ferritin content in the substantia nigra of normal subjects at different ages: consequences for iron storage and neurodegenerative processes. Journal of Neurochemistry 2001 76 6 1766 1773 2-s2.0-0035103932 10.1046/j.1471-4159.2001.00186.x (Pubitemid 32221116)
4. Lhermitte J., Kraus W. M., McAlpine D., On the occurrence of abnormal deposits of iron in the brain in parkinsonism with special reference to its localisation. Journal of Neurology, Neurosurgery & Psychiatry 1924 195 s1 s5
5. Berg D., Grote C., Rausch W.-D., Mäurer M., Wesemann W., Riederer P., Becker G., Iron accumulation in the substantia nigra in rats visualized by ultrasound. Ultrasound in Medicine and Biology 1999 25 6 901 904 2-s2.0-0032765888 10.1016/S0301-5629(99)00046-0 (Pubitemid 29325763)
6. Berg D., Roggendorf W., Schröder U., Klein R., Tatschner T., Benz P., Tucha O., Preier M., Lange K. W., Reiners K., Gerlach M., Becker G., Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. Archives of Neurology 2002 59 6 999 1005 2-s2.0-0036279410 (Pubitemid 34640761)
7. Zecca L., Berg D., Arzberger T., Ruprecht P., Rausch W. D., Musicco M., Tampellini D., Riederer P., Gerlach M., Becker G., In vivo detection of iron and neuromelanin by transcranial sonography: a new approach for early detection of substantia nigra damage. Movement Disorders 2005 20 10 1278 1285 2-s2.0-27844547163 10.1002/mds.20550 (Pubitemid 41645902)
8. Berg D., In vivo detection of iron and neuromelanin by transcranial sonography-a new approach for early detection of substantia nigra damage. Journal of Neural Transmission 2006 113 6 775 780 2-s2.0-33744901442 10.1007/s00702-005-0447-5 (Pubitemid 43847171)
9. Berg D., Hochstrasser H., Schweitzer K. J., Riess O., Disturbance of iron metabolism in Parkinson's disease-ultrasonography as a biomarker. Neurotoxicity Research 2006 9 1 1 13 2-s2.0-33645929729 10.1007/BF03033302
10. Prestel J., Schweitzer K. J., Hofer A., Gasser T., Berg D., Predictive value of transcranial sonography in the diagnosis of Parkinson's disease. Movement Disorders 2006 21 10 1763 1765 2-s2.0-33751011877 10.1002/mds.21054 (Pubitemid 44742216)
11. Becker G., Seufert J., Bogdahn U., Reichmann H., Reiners K., Degeneration of substantia nigra in chronic Parkinson's disease visualized by transcranial color-coded real-time sonography. Neurology 1995 45 1 182 184 2-s2.0-0028869760
12. Berg D., Transcranial ultrasound as a risk marker for Parkinson's disease. Movement Disorders 2009 24 supplement 2 S677 S683 2-s2.0-72849145914 10.1002/mds.22540
13. Behnke S., Schroeder U., Dillmann U., Buchholz H. G., Schreckenberger M., Fuss G., Reith W., Berg D., Krick C. M., Hyperechogenicity of the substantia nigra in healthy controls is related to MRI changes and to neuronal loss as determined by F-Dopa PET. NeuroImage 2009 47 4 1237 1243 2-s2.0-67651161861 10.1016/j.neuroimage.2009.05.072
14. Berg D., Siefker C., Ruprecht-Dörfler P., Becker G., Relationship of substantia nigra echogenicity and motor function in elderly subjects. Neurology 2001 56 1 13 17 2-s2.0-0035830425 (Pubitemid 32059645)
15. Berg D., Seppi K., Behnke S., Liepelt I., Schweitzer K., Stockner H., Wollenweber F., Gaenslen A., Mahlknecht P., Spiegel J., Godau J., Huber H., Srulijes K., Kiechl S., Bentele M., Gasperi A., Schubert T., Hiry T., Probst M., Schneider V., Klenk J., Sawires M., Willeit J., Maetzler W., Fassbender K., Gasser T., Poewe W., Enlarged substantia Nigra hyperechogenicity and risk for Parkinson disease: a 37-month 3-center study of 1847 older persons. Archives of Neurology 2011 68 7 932 937 2-s2.0-79960173762 10.1001/archneurol.2011.141
16. Gelman N., Gorell J. M., Barker P. B., Savage R. M., Spickler E. M., Windham J. P., Knight R. A., MR imaging of human brain at 3.0 T: preliminary report on transverse relaxation rates and relation to estimated iron content. Radiology 1999 210 3 759 767 2-s2.0-0033013737 (Pubitemid 29124039)
17. Gorell G., Increased iron-related MRI contrast in the substantia nigra in Parkinson's disease. Neurology 1995 45 7 1138 1143 2-s2.0-0029090258
18. Atasoy H. T., Nuyan O., Tunc T., Yorubulut M., Unal A. E., Inan L. E., T2-weighted MRI in Parkinson's disease; substantia nigra pars compacta hypointensity correlates with the clinical scores. Neurology India 2004 52 3 332 337 2-s2.0-7244242355 (Pubitemid 39430186)
19. Ryvlin P., Broussolle E., Piollet H., Viallet F., Khalfallah Y., Chazot G., Magnetic resonance imaging evidence of decreased putamenal iron content in idiopathic Parkinson's disease. Archives of Neurology 1995 52 6 583 588 2-s2.0-0029054075
20. Ulla M., Marie Bonny J., Ouchchane L., Is r2- a new MRI biomarker for the progression of Parkinson's disease? A longitudinal follow-up. PloS ONE 2013 8 e57904
21. Menke R. A., Scholz J., Miller K. L., Deoni S., Jbabdi S., Matthews P. M., Zarei M., MRI characteristics of the substantia nigra in Parkinson's disease: a combined quantitative T1 and DTI study. NeuroImage 2009 47 2 435 441 2-s2.0-67349215018 10.1016/j.neuroimage.2009.05.017
22. Osaki S., Johnson D. A., Frieden E., The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum. The Journal of Biological Chemistry 1966 241 12 2746 2751 2-s2.0-0014027719
23. Miyajima H., Nishimura Y., Mizoguchi K., Familial apoceruloplasmin deficiency associated with blepharospasm and retinal degeneration. Neurology 1987 37 5 761 767 2-s2.0-0023240051 (Pubitemid 17064662)
24. Yoshida K., Furihata K., Takeda S., Nakamura A., Yamamoto K., Morita H., Hiyamuta S., Ikeda S., Shimizu N., Yanagisawa N., A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nature Genetics 1995 9 3 267 272 2-s2.0-0028895749
25. Patel B. N., Dunn R. J., Jeong S. Y., Zhu Q., Julien J.-P., David S., Ceruloplasmin regulates iron levels in the CNS and prevents free radical injury. Journal of Neuroscience 2002 22 15 6578 6586 2-s2.0-0036703490 (Pubitemid 35386414)
26. Ayton S., Lei P., Duce J. A., Ceruloplasmin dysfunction and therapeutic potential for parkinson disease. Annals of Neurology 2013 73 article 554
27. Harris Z. L., Durley A. P., Man T. K., Gitlin J. D., Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proceedings of the National Academy of Sciences of the United States of America 1999 96 19 10812 10817 2-s2.0-0032875387 10.1073/pnas.96.19.10812 (Pubitemid 29442226)
28. McNeill A., Pandolfo M., Kuhn J., Shang H., Miyajima H., The neurological presentation of ceruloplasmin gene mutations. European Neurology 2008 60 4 200 205 2-s2.0-48049107099 10.1159/000148691
29. Hochstrasser H., Tomiuk J., Walter U., Functional relevance of ceruloplasmin mutations in Parkinson's disease. The FASEB Journal 2005 19 article 1851
30. Hochstrasser H., Bauer P., Walter U., Behnke S., Spiegel J., Csoti I., Zeiler B., Bornemann A., Pahnke J., Becker G., Riess O., Berg D., Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease. Neurology 2004 63 10 1912 1917 2-s2.0-5444246509 (Pubitemid 39532390)
31. Kotzbauer P. T., Truax A. C., Trojanowski J. Q., Lee V. M.-Y., Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2. Journal of Neuroscience 2005 25 3 689 698 2-s2.0-12744280679 10.1523/JNEUROSCI.4265-04.2005
32. Swaiman K. F., Hallervorden-Spatz syndrome and brain iron metabolism. Archives of Neurology 1991 48 12 1285 1293 2-s2.0-0026317374
33. Alberca R., Rafel E., Chinchon I., Vadillo J., Navarro A., Late onset Parkinsonian syndrome in Hallervorden-Spatz disease. Journal of Neurology Neurosurgery and Psychiatry 1987 50 12 1665 1668 2-s2.0-0023614374 (Pubitemid 18096677)
34. Arawaka S., Saito Y., Murayama S., Mori H., Lewy body in neurodegeneration with brain iron accumulation type 1 is immunoreactive for α -synuclein. Neurology 1998 51 3 887 889 2-s2.0-0031721278 (Pubitemid 28449283)
35. Tofaris G. K., Revesz T., Jacques T. S., Papacostas S., Chataway J., Adult-onset neurodegeneration with brain iron accumulation and cortical α -synuclein and tau pathology: a distinct clinicopathological entity. Archives of Neurology 2007 64 2 280 282 2-s2.0-33846989334 10.1001/archneur.64.2.280
36. Galvin J. E., Giasson B., Hurtig H. I., Lee V. M.-Y., Trojanowski J. Q., Neurodegeneration with brain iron accumulation, type 1 is characterized by α -, β -, and γ -synuclein neuropathology. The American Journal of Pathology 2000 157 2 361 368 2-s2.0-0033897735 (Pubitemid 30626903)
37. Curtis A. R. J., Fey C., Morris C. M., Bindoff L. A., Ince P. G., Chinnery P. F., Coulthard A., Jackson M. J., Jackson A. P., McHale D. P., Hay D., Barker W. A., Markham A. F., Bates D., Curtis A., Burn J., Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nature Genetics 2001 28 4 350 354 2-s2.0-0034941118 10.1038/ng571 (Pubitemid 32702424)
38. Vidal R., Ghetti B., Takao M., Brefel-Courbon C., Uro-Coste E., Glazier B. S., Siani V., Benson M. D., Calvas P., Miravalle L., Rascol O., Delisle M. B., Intracellular ferritin accumulation in neural and extraneural tissue characterizes a neurodegenerative disease associated with a mutation in the ferritin light polypeptide gene. Journal of Neuropathology and Experimental Neurology 2004 63 4 363 380 2-s2.0-12144288949 (Pubitemid 38429033)
39. Mancuso M., Davidzon G., Kurlan R. M., Tawil R., Bonilla E., Di Mauro S., Powers J. M., Hereditary ferritinopathy: a novel mutation, its cellular pathology, and pathogenetic insights. Journal of Neuropathology and Experimental Neurology 2005 64 4 280 294 2-s2.0-16844363930 (Pubitemid 40489555)
40. Maciel P., Cruz V. T., Constante M., Iniesta I., Costa M. C., Gallati S., Sousa N., Sequeiros J., Coutinho P., Santos M. M., Neuroferritinopathy: missense mutation in FTL causing early-onset bilateral pallidal involvement. Neurology 2005 65 4 603 605 2-s2.0-23844553465 10.1212/01.wnl.0000178224.81169. c2 (Pubitemid 41170724)
41. Ohta E., Nagasaka T., Shindo K., Toma S., Nagasaka K., Ohta K., Shiozawa Z., Neuroferritinopathy in a Japanese family with a duplication in the ferritin light chain gene. Neurology 2008 70 16 1493 1494 2-s2.0-42049109697 10.1212/01.wnl.0000310428.74624.95 (Pubitemid 351521946)
42. Devos D., Tchofo P. J., Vuillaume I., Deste A., Batey S., Burn J., Chinnery P. F., Clinical features and natural history of neuroferritinopathy caused by the 458dupA FTL mutation. Brain 2009 132 6, article e109 2-s2.0-67649414590 10.1093/brain/awn274
43. Kunota A., Hida A., Ichikawa Y., Momose Y., Goto J., Igeta Y., Hashida H., Yoshida K., Ikeda S.-I., Kanazawa I., Tsuji S., A novel ferritin light chain gene mutation in a Japanese family with neuroferritinopathy: description of clinical features and implications for genotype-phenotype correlations. Movement Disorders 2009 24 3 441 445 2-s2.0-67651103065 10.1002/mds.22435
44. Ben-Shachar D., Youdim M. B. H., Intranigral iron injection induces behavioral and biochemical "Parkinsonism" in rats. Journal of Neurochemistry 1991 57 6 2133 2135 2-s2.0-0025824668 (Pubitemid 21922868)
45. Dal-Pizzol F., Klamt F., Frota M.L.C. J., Andrades M. E., Caregnato F. F., Vianna M. M. R., Schröder N., Quevedo J., Izquierdo I., Archer T., Moreira J. C. F., Neonatal iron exposure induces oxidative stress in adult Wistar rat. Developmental Brain Research 2001 130 1 109 114 2-s2.0-17944376584 10.1016/S0165-3806(01)00218-8 (Pubitemid 32830978)
46. Budni P., De Lima M. N. M., Polydoro M., Moreira J. C. F., Schroder N., Dal-Pizzol F., Antioxidant effects of selegiline in oxidative stress induced by iron neonatal treatment in rats. Neurochemical Research 2007 32 6 965 972 2-s2.0-34248159387 10.1007/s11064-006-9249-x (Pubitemid 46726015)
47. Kaur D., Peng J., Chinta S. J., Rajagopalan S., Di Monte D. A., Cherny R. A., Andersen J. K., Increased murine neonatal iron intake results in Parkinson-like neurodegeneration with age. Neurobiology of Aging 2007 28 6 907 913 2-s2.0-34247116462 10.1016/j.neurobiolaging.2006.04.003 (Pubitemid 46589736)
48. Lan J., Jiang D. H., Desferrioxamine and vitamin E protect against iron and MPTP-induced neurodegeneration in mice. Journal of Neural Transmission 1997 104 4-5 469 481 2-s2.0-0030864433 10.1007/BF01277665 (Pubitemid 27379903)
49. Temlett J. A., Landsberg J. P., Watt F., Grime G. W., Increased iron in the substantia nigra compacta of the MPTP-lesioned hemiparkinsonian African Green monkey: evidence from proton microprobe elemental microanalysis. Journal of Neurochemistry 1994 62 1 134 146 2-s2.0-0028045734
50. Jiang H., Chen W.-F., Xie J.-X., Relationship between dopamine and iron contents in the brain of Parkinsonian rats. Acta Physiologica Sinica 2001 53 5 334 338 2-s2.0-1542650720 (Pubitemid 33696489)
51. Liang L.-P., Patel M., Iron-sulfur enzyme mediated mitochondrial superoxide toxicity in experimental Parkinson's disease. Journal of Neurochemistry 2004 90 5 1076 1084 2-s2.0-4444360218 10.1111/j.1471-4159.2004. 02567.x (Pubitemid 39167341)
52. Kaur D., Yantiri F., Rajagopalan S., Kumar J., Mo J. Q., Boonplueang R., Viswanath V., Jacobs R., Yang L., Beal M. F., DiMonte D., Volitaskis I., Ellerby L., Cherny R. A., Bush A. I., Andersen J. K., Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron 2003 37 6 899 909 2-s2.0-0242684415 10.1016/S0896-6273(03)00126-0 (Pubitemid 36398297)
53. Shachar D. B., Kahana N., Kampel V., Warshawsky A., Youdim M. B. H., Neuroprotection by a novel brain permeable iron chelator, VK-28, against 6-hydroxydopamine lession in rats. Neuropharmacology 2004 46 2 254 263 2-s2.0-0346849912 10.1016/j.neuropharm.2003.09.005 (Pubitemid 37532833)
54. Barnham K. J., Masters C. L., Bush A. I., Neurodegenerative diseases and oxidatives stress. Nature Reviews Drug Discovery 2004 3 3 205 214 2-s2.0-1642308134 (Pubitemid 38379987)
55. Dexter D. T., Carter C. J., Wells F. R., Javoy-Agid F., Agid Y., Lees A., Jenner P., Marsden C. D., Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. Journal of Neurochemistry 1989 52 2 381 389 2-s2.0-0024585155 (Pubitemid 19037600)
56. Alam Z. I., Jenner A., Daniel S. E., Lees A. J., Cairns N., Marsden C. D., Jenner P., Halliwell B., Oxidative DNA damage in the Parkinsonian brain: an apparent selective increase in 8-hydroxyguanine levels in substantia nigra. Journal of Neurochemistry 1997 69 3 1196 1203 2-s2.0-0030878073 (Pubitemid 27364841)
57. Sian J., Dexter D. T., Lees A. J., Daniel S., Agid Y., Javoy-Agid F., Jenner P., Marsden C. D., Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Annals of Neurology 1994 36 3 348 355 2-s2.0-0028075410 (Pubitemid 24280055)
58. Polymeropoulos M. H., Lavedan C., Leroy E., Ide S. E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R., Stenroos E. S., Chandrasekharappa S., Athanassiadou A., Papapetropoulos T., Johnson W. G., Lazzarini A. M., Duvoisin R. C., Di Iorio G., Golbe L. I., Nussbaum R. L., Mutation in the α -synuclein gene identified in families with Parkinson's disease. Science 1997 276 5321 2045 2047 2-s2.0-0030744876 10.1126/science.276.5321.2045 (Pubitemid 27443610)
59. Krüger R., Kuhn W., Müller T., Woitalla D., Graeber M., Kösel S., Przuntek H., Epplen J. T., Schöls L., Riess O., Ala30Pro mutation in the gene encoding α -synuclein in Parkinson's disease. Nature Genetics 1998 18 2 106 108 2-s2.0-0031990490
60. Zarranz J. J., Alegre J., Gómez-Esteban J. C., Lezcano E., Ros R., Ampuero I., Vidal L., Hoenicka J., Rodriguez O., Atarés B., Llorens V., Gomez Tortosa E., Del Ser T., Muñoz D. G., De Yebenes J. G., The new mutation, E46K, of α -synuclein causes parkinson and lewy body dementia. Annals of Neurology 2004 55 2 164 173 2-s2.0-10744230149 10.1002/ana.10795 (Pubitemid 38166992)
61. Chartier-Harlin M.-C., Kachergus J., Roumier C., Mouroux V., Douay X., Lincoln S., Levecque C., Larvor L., Andrieux J., Hulihan M., Waucquier N., Defebvre L., Amouyel P., Farrer M., Destée A., α -synuclein locus duplication as a cause of familial Parkinson's disease. The Lancet 2004 364 9440 1167 1169 2-s2.0-4644290985 10.1016/S0140-6736(04)17103-1 (Pubitemid 39296604)
62. Miller D. W., Hague S. M., Clarimon J., Baptista M., Gwinn-Hardy K., Cookson M. R., Singleton A. B., α -synuclein in blood and brain from familial Parkinson disease with SNCA locus triplication. Neurology 2004 62 10 1835 1838 2-s2.0-2442700253 (Pubitemid 38661745)
63. Spillantini M. G., Schmidt M. L., Lee V. M.-Y., Trojanowski J. Q., Jakes R., Goedert M., α -synuclein in Lewy bodies. Nature 1997 388 6645 839 840 2-s2.0-0030882856 10.1038/42166 (Pubitemid 27377048)
64. Bharathi B., Indi S. S., Rao K. S. J., Copper- and iron-induced differential fibril formation in α -synuclein: TEM study. Neuroscience Letters 2007 424 2 78 82 2-s2.0-34548021006 10.1016/j.neulet.2007.06.052 (Pubitemid 47285498)
65. Bharathi B., Rao K. S. J., Thermodynamics imprinting reveals differential binding of metals to α -synuclein: relevance to parkinson's disease. Biochemical and Biophysical Research Communications 2007 359 1 115 120 2-s2.0-34249669709 10.1016/j.bbrc.2007.05.060 (Pubitemid 46836676)
66. Peng Y., Wang C., Xu H. H., Liu Y.-N., Zhou F., Binding of α -synuclein with Fe(III) and with Fe(II) and biological implications of the resultant complexes. Journal of Inorganic Biochemistry 2010 104 4 365 370 2-s2.0-77049084488 10.1016/j.jinorgbio.2009.11.005
67. Paik S. R., Shin H.-J., Lee J.-H., Metal-catalyzed oxidation of α -synuclein in the presence of copper(II) and hydrogen peroxide. Archives of Biochemistry and Biophysics 2000 378 2 269 277 2-s2.0-0034660568 10.1006/abbi.2000.1822 (Pubitemid 30397627)
68. Golts N., Snyder H., Frasier M., Theisler C., Choi P., Wolozin B., Magnesium inhibits spontaneous and iron-induced aggregation of α -synuclein. The Journal of Biological Chemistry 2002 277 18 16116 16123 2-s2.0-0037013194 10.1074/jbc.M107866200 (Pubitemid 34967897)
69. Turnbull S., Tabner B. J., El-Agnaf O. M. A., Moore S., Davies Y., Allsop D., α -synuclein implicated in Parkinson's disease catalyses the formation of hydrogen peroxide in vitro. Free Radical Biology and Medicine 2001 30 10 1163 1170 2-s2.0-0035873812 10.1016/S0891-5849(01)00513-5 (Pubitemid 32441842)
70. He Q., Song N., Xu H., Wang R., Xie J., Jiang H., Alpha-synuclein aggregation is involved in the toxicity induced by ferric iron to SK-N-SH neuroblastoma cells. Journal of Neural Transmission 2011 118 3 397 406 2-s2.0-80051633055 10.1007/s00702-010-0453-0
71. Li W.-J., Jiang H., Song N., Xie J.-X., Dose- and time-dependent α -synuclein aggregation induced by ferric iron in SK-N-SH cells. Neuroscience Bulletin 2010 26 3 205 210 2-s2.0-77955978437 10.1007/s12264-010-1117-7
72. Ostrerova-Golts N., Petrucelli L., Hardy J., Lee J. M., Farer M., Wolozin B., The A53T α -synuclein mutation increases iron-dependent aggregation and toxicity. Journal of Neuroscience 2000 20 16 6048 6054 2-s2.0-0034663039 (Pubitemid 30658398)
73. Li W., Jiang H., Song N., Xie J., Oxidative stress partially contributes to iron-induced alpha-synuclein aggregation in SK-N-SH cells. Neurotoxicity Research 2011 19 3 435 442 2-s2.0-79951950516 10.1007/s12640-010-9187-x
74. Castellani R. J., Siedlak S. L., Perry G., Smith M. A., Sequestration of iron by Lewy bodies in Parkinson's disease. Acta Neuropathologica 2000 100 2 111 114 2-s2.0-0033947467 (Pubitemid 30456131)
75. Zayed J., Ducic S., Campanella G., Panisset J. C., Andre P., Masson H., Roy M., Environmental factors in the etiology of Parkinson's disease. Canadian Journal of Neurological Sciences 1990 17 3 286 291 2-s2.0-0025192139 (Pubitemid 20254751)
76. Logroscino G., Marder K., Graziano J., Freyer G., Slavkovich V., Lojacono N., Cote L., Mayeux R., Dietary iron, animal fats, and risk of Parkinson's disease. Movement Disorders 1998 13 supplement 1 13 16 2-s2.0-0031922955
77. Morgan E. H., Moos T., Mechanism and developmental changes in iron transport across the blood-brain barrier. Developmental Neuroscience 2002 24 2-3 106 113 2-s2.0-0036967837 10.1159/000065699 (Pubitemid 36151440)
78. Chen J. H., Shahnavas S., Singh N., Ong W. Y., Walczyk T., Stable iron isotope tracing reveals significant brain iron uptake in adult rats. Metallomics 2013 5 article 167
79. Dallman P. R., Siimes M. A., Manies E. C., Brain iron: persistent deficiency following short term iron deprivation in the young rat. British Journal of Haematology 1975 31 2 209 215 2-s2.0-0016742687
80. Dallman P. R., Spirito R. A., Brain iron in the rat: extremely slow turnover in normal rats may explain long lasting effects of early iron deficiency. Journal of Nutrition 1977 107 6 1075 1081 2-s2.0-0017394748 (Pubitemid 8129636)
81. Ben-Shachar D., Ashkenazi R., Youdim M. B. H., Long-term consequence of early iron-deficiency on dopaminergic neurotransmission in rats. International Journal of Developmental Neuroscience 1986 4 1 81 88 2-s2.0-0022654236 (Pubitemid 16126592)
82. Ayton S., Lei P., Bush A. I., Metallostasis in Alzheimer's disease. Free Radical Biolology and Medicine 2013 62 76 89 10.1016/j.freeradbiomed.2012.10.558
83. Hare D., Ayton S., Bush A., Lei P., A delicate balance: iron metabolism and diseases of the brain. Frontiers in Aging Neuroscience 2013 5 34
84. Dexter D. T., Carayon A., Vidailhet M., Ruberg M., Agid F., Agid Y., Lees A. J., Wells F. R., Jenner P., Marsden C. D., Decreased ferritin levels in brain in Parkinson's disease. Journal of Neurochemistry 1990 55 1 16 20 2-s2.0-0025374969 10.1111/j.1471-4159.1990.tb08814.x (Pubitemid 20187798)
85. Faucheux B. A., Hauw J.-J., Agid Y., Hirsch E. C., The density of [125I]-transferrin binding sites on perikarya of melanized neurons of the substantia nigra is decreased in Parkinson's disease. Brain Research 1997 749 1 170 174 2-s2.0-0030615199 10.1016/S0006-8993(96)01412-6 (Pubitemid 27096473)
86. He Y., Lee T., Leong S. K., Time course of dopaminergic cell death and changes in iron, ferritin and transferrin levels in the rat substantia nigra after 6-hydroxydopamine (6-OHDA) lesioning. Free Radical Research 1999 31 2 103 112 2-s2.0-0032870588 10.1080/10715769900301611 (Pubitemid 29425470)
87. Dekker M. C. J., Giesbergen P. C., Njajou O. T., Van Swieten J. C., Hofman A., Breteler M. M. B., Van Duijn C. M., Mutations in the hemochromatosis gene (HFE), Parkinson's disease and parkinsonism. Neuroscience Letters 2003 348 2 117 119 2-s2.0-0041696494 10.1016/S0304-3940(03)00713-4 (Pubitemid 36936973)
88. Guerreiro R. J., Bras J. M., Santana I., Januario C., Santiago B., Morgadinho A. S., Ribeiro M. H., Hardy J., Singleton A., Oliveira C., Association of HFE common mutations with Parkinson's disease, Alzheimer's disease and mild cognitive impairment in a Portuguese cohort. BMC Neurology 2006 6, article 24 2-s2.0-33747179546 10.1186/1471-2377-6-24 (Pubitemid 44227550)
89. Akbas N., Hochstrasser H., Deplazes J., Tomiuk J., Bauer P., Walter U., Behnke S., Riess O., Berg D., Screening for mutations of the HFE gene in Parkinson's disease patients with hyperechogenicity of the substantia nigra. Neuroscience Letters 2006 407 1 16 19 2-s2.0-33748427682 10.1016/j.neulet.2006. 07.070 (Pubitemid 44345006)
90. Biasiotto G., Goldwurm S., Finazzi D., Tunesi S., Zecchinelli A., Sironi F., Pezzoli G., Arosio P., HFE gene mutations in a population of Italian Parkinson's disease patients. Parkinsonism and Related Disorders 2008 14 5 426 430 2-s2.0-47049124541 10.1016/j.parkreldis.2007.10.011
91. Aamodt A. H., Stovner L. J., Thorstensen K., Lydersen S., White L. R., Aasly J. O., Prevalence of haemochromatosis gene mutations in Parkinson's disease. Journal of Neurology, Neurosurgery and Psychiatry 2007 78 3 315 317 2-s2.0-33847734350 10.1136/jnnp.2006.101352 (Pubitemid 46579674)
92. Bastin J. M., Jones M., O'Callaghan C. A., Schimanski L., Mason D. Y., Townsend A. R. M., Kupffer cell staining by an HFE-specific monoclonal antibody: implications for hereditary haemochromatosis. British Journal of Haematology 1998 103 4 931 941 2-s2.0-0032427653 10.1046/j.1365-2141.1998.01102.x (Pubitemid 29012627)
93. Mastroberardino P. G., Hoffman E. K., Horowitz M. P., Betarbet R., Taylor G., Cheng D., Na H. M., Gutekunst C.-A., Gearing M., Trojanowski J. Q., Anderson M., Chu C. T., Peng J., Greenamyre J. T., A novel transferrin/TfR2- mediated mitochondrial iron transport system is disrupted in Parkinson's disease. Neurobiology of Disease 2009 34 3 417 431 2-s2.0-67349106731 10.1016/j.nbd.2009.02.009
94. Song N., Jiang H., Wang J., Xie J.-X., Divalent metal transporter 1 up-regulation is involved in the 6-hydroxydopamine-induced ferrous iron influx. Journal of Neuroscience Research 2007 85 14 3118 3126 2-s2.0-35848961208 10.1002/jnr.21430 (Pubitemid 350057367)
95. Jiang H., Qian Z.-M., Xie J.-X., Increased DMT1 expression and iron content in MPTP-treated C57BL/6 mice. Acta Physiologica Sinica 2003 55 5 571 576 2-s2.0-0242712032 (Pubitemid 37370020)
96. Salazar J., Mena N., Hunot S., Prigent A., Alvarez-Fischer D., Arredondo M., Duyckaerts C., Sazdovitch V., Zhao L., Garrick L. M., Nuñez M. T., Garrick M. D., Raisman-Vozari R., Hirsch E. C., Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America 2008 105 47 18578 18583 2-s2.0-57449092273 10.1073/pnas.0804373105
97. Donovan A., Lima C. A., Pinkus J. L., Pinkus G. S., Zon L. I., Robine S., Andrews N. C., The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metabolism 2005 1 3 191 200 2-s2.0-20444416123 10.1016/j.cmet.2005.01.003 (Pubitemid 43960600)
98. Hellman N. E., Gitlin J. D., Ceruloplasmin metabolism and function. Annual Review of Nutrition 2002 22 439 458 2-s2.0-0036400025 10.1146/annurev.nutr.22.012502.114457 (Pubitemid 35221468)
99. Boll M.-C., Alcaraz-Zubeldia M., Montes S., Rios C., Free copper, ferroxidase and SOD1 activities, lipid peroxidation and NOx content in the CSF. A different marker profile in four neurodegenerative diseases. Neurochemical Research 2008 33 9 1717 1723 2-s2.0-48449094910 10.1007/s11064-008-9610-3
100. Boll M.-C., Sotelo J., Otero E., Alcaraz-Zubeldia M., Rios C., Reduced ferroxidase activity in the cerebrospinal fluid from patients with Parkinson's disease. Neuroscience Letters 1999 265 3 155 158 2-s2.0-0033597299 10.1016/S0304-3940(99)00221-9 (Pubitemid 29207389)
101. Olivieri S., Conti A., Iannaccone S., Cannistraci C. V., Campanella A., Barbariga M., Codazzi F., Pelizzoni I., Magnani G., Pesca M., Franciotta D., Cappa S. F., Alessio M., Ceruloplasmin oxidation, a feature of parkinson's disease CSF, inhibits ferroxidase activity and promotes cellular iron retention. Journal of Neuroscience 2011 31 50 18568 18577 2-s2.0-83455177604 10.1523/JNEUROSCI.3768-11.2011
102. Martínez-Hernández R., Montes S., Higuera-Calleja J., Yescas P., Boll M.-C., Diaz-Ruiz A., Rios C., Plasma ceruloplasmin ferroxidase activity correlates with the nigral sonographic area in Parkinson's disease patients: a pilot study. Neurochemical Research 2011 36 11 2111 2115 2-s2.0-80054992416 10.1007/s11064-011-0535-x
103. Bharucha K. J., Friedman J. K., Vincent A. S., Ross E. D., Lower serum ceruloplasmin levels correlate with younger age of onset in Parkinson's disease. Journal of Neurology 2008 255 12 1957 1962 2-s2.0-67349173208 10.1007/s00415-009-0063-7
104. Tórsdóttir G., Kristinsson J., Sveinbjörnsdó ttir S., Snaedal J., Jóhannesson T., Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease. Pharmacology and Toxicology 1999 85 5 239 243 2-s2.0-0032734745
105. Jin L., Wang J., Zhao L., Jin H., Fei G., Zhang Y., Zeng M., Zhong C., Decreased serum ceruloplasmin levels characteristically aggravate nigral iron deposition in Parkinson's disease. Brain 2011 134 1 50 58 2-s2.0-78650695967 10.1093/brain/awq319
106. Jin L., Wang J., Jin H., Fei G., Zhang Y., Chen W., Zhao L., Zhao N., Sun X., Zeng M., Zhong C., Nigral iron deposition occurs across motor phenotypes of Parkinson's disease. European Journal of Neurology 2012 19 7 969 976 2-s2.0-84856250254 10.1111/j.1468-1331.2011.03658.x
107. Tórsdóttir G., Sveinbjörnsdóttir S., Kristinsson J., Snaedal J., Jóhannesson T., Ceruloplasmin and superoxide dismutase (SOD1) in Parkinson's disease: a follow-up study. Journal of the Neurological Sciences 2006 241 1-2 53 58 2-s2.0-30944455439 10.1016/j.jns.2005. 10.015 (Pubitemid 43112516)
108. Loeffler D. A., LeWitt P. A., Juneau P. L., Sima A. A. F., Nguyen H.-U., DeMaggio A. J., Brickman C. M., Brewer G. J., Dick R. D., Troyer M. D., Kanaley L., Increased regional brain concentrations of ceruloplasmin in neurodegenerative disorders. Brain Research 1996 738 2 265 274 2-s2.0-0030569306 10.1016/S0006-8993(96)00782-2 (Pubitemid 26378921)
109. Lei P., Ayton S., Finkelstein D. I., Adlard P. A., Masters C. L., Bush A. I., Tau protein: relevance to Parkinson's disease. International Journal of Biochemistry and Cell Biology 2010 42 11 1775 1778 2-s2.0-77957260958 10.1016/j.biocel.2010.07.016
110. Lei P., Ayton S., Finkelstein D. I., Spoerri L., Ciccotosto G. D., Wright D. K., Wong B. X. W., Adlard P. A., Cherny R. A., Lam L. Q., Roberts B. R., Volitakis I., Egan G. F., McLean C. A., Cappai R., Duce J. A., Bush A. I., Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nature Medicine 2012 18 2 291 295 2-s2.0-84856708923 10.1038/nm.2613
111. Duce J. A., Tsatsanis A., Cater M. A., James S. A., Robb E., Wikhe K., Leong S. L., Perez K., Johanssen T., Greenough M. A., Cho H.-H., Galatis D., Moir R. D., Masters C. L., McLean C., Tanzi R. E., Cappai R., Barnham K. J., Ciccotosto G. D., Rogers J. T., Bush A. I., Iron-export ferroxidase activity of β -amyloid precursor protein is inhibited by zinc in Alzheimer's disease. Cell 2010 142 6 857 867 2-s2.0-77956647381 10.1016/j.cell.2010.08.014
112. Kalinowski D. S., Richardson D. R., The evolution of iron chelators for the treatment of iron overload disease and cancer. Pharmacological Reviews 2005 57 4 547 583 2-s2.0-29844457587 10.1124/pr.57.4.2 (Pubitemid 43036441)
113. Devos D., Moreau C., Devedjian J. C., Kluza J., Laloux C., Jonneaux A., Petrault M., Ryckewaert G., Garçon G., Rouaix N., Duhamel A., Jissendi P., Dujardin K., Auger F., Ravasi L., Hopes L., Grolez G., Firdaus W., Sablonnière B., Strubi-Vuillaume I., Zahr N., Destée A., Corvol J. C., Pöltl D., Leist M., Rose C., Defebvre L., Marchetti P., Cabantchik I. Z., Bordet R., Targeting chelatable iron as a therapeutic modality in Parkinson's disease. Antioxidants and Redox Signaling 10.1089/ars.2013.5666
114. Habgood M. D., Liu Z. D., Dehkordi L. S., Khodr H. H., Abbott J., Hider R. C., Investigation into the correlation between the structure of hydroxypyridinones and blood-brain barrier permeability. Biochemical Pharmacology 1999 57 11 1305 1310 2-s2.0-0033152287 10.1016/S0006-2952(99)00031- 3 (Pubitemid 29185152)
115. Gal S., Zheng H., Fridkin M., Youdim M. B. H., Restoration of nigrostriatal dopamine neurons in post-MPTP treatment by the novel multifunctional brain-permeable iron chelator-monoamine oxidase inhibitor drug, M30. Neurotoxicity Research 2010 17 1 15 27 2-s2.0-77449119388 10.1007/s12640-009-9070-9
116. Dexter D. T., Wells F. R., Agid F., Agid Y., Lees A. J., Jenner P., Marsden C. D., Increased nigral iron content in postmortem Parkinsonian brain. The Lancet 1987 2 8569 1219 1220 2-s2.0-0023638828 (Pubitemid 17156630)
117. Sofic E., Riederer P., Heinsen H., Beckmann H., Reynolds G. P., Hebenstreit G., Youdim M. B. H., Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. Journal of Neural Transmission 1988 74 3 199 205 2-s2.0-0023804321
118. Riederer P., Sofic E., Rausch W.-D., Schmidt B., Reynolds G. P., Jellinger K., Youdim M. B. H., Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. Journal of Neurochemistry 1989 52 2 515 520 2-s2.0-0024557734 (Pubitemid 19037617)
119. Uitti R. J., Rajput A. H., Rozdilsky B., Bickis M., Wollin T., Yuen W. K., Regional metal concentrations in Parkinson's disease, other chronic neurological diseases, and control brains. Canadian Journal of Neurological Sciences 1989 16 3 310 314 2-s2.0-0024339772 (Pubitemid 19213592)
120. Dexter D. T., Wells F. R., Lees A. J., Agid F., Agid Y., Jenner P., Marsden C. D., Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson's disease. Journal of Neurochemistry 1989 52 6 1830 1836 2-s2.0-0024356620 (Pubitemid 19140770)
121. Dexter D. T., Carayon A., Javoy-Agid F., Agid Y., Wells F. R., Daniel S.
122. Hirsch E. C., Brandel J.-P., Galle P., Javoy-Agid F., Agid Y., Iron and aluminum increase in the substantia nigra of patients with Parkinson's disease: an X-ray microanalysis. Journal of Neurochemistry 1991 56 2 446 451 2-s2.0-0026034279 10.1111/j.1471-4159.1991.tb08170.x (Pubitemid 21901982)
123. Sofic E., Paulus W., Jellinger K., Riederer P., Youdim M. B. H., Selective increase of iron in substantia nigra zona compacta of Parkinsonian brains. Journal of Neurochemistry 1991 56 3 978 982 2-s2.0-0025963530 (Pubitemid 21922711)
124. Good P. F., Olanow C. W., Perl D. P., Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson's disease: a LAMMA study. Brain Research 1992 593 2 343 346 2-s2.0-0026746512 10.1016/0006-8993(92)91334-B
125. Mann V. M., Cooper J. M., Daniel S. E., Srai K., Jenner P., Marsden C. D., Schapira A. H. V., Complex I, iron, and ferritin in Parkinson's disease substantia nigra. Annals of Neurology 1994 36 6 876 881 2-s2.0-0027995435 10.1002/ana.410360612 (Pubitemid 24370927)
126. Loeffler D. A., Connor J. R., Juneau P. L., Snyder B. S., Kanaley L., DeMaggio A. J., Nguyen H., Brickman C. M., LeWitt P. A., Transferrin and iron in normal, Alzheimer's disease, and Parkinson's disease brain regions. Journal of Neurochemistry 1995 65 2 710 716 2-s2.0-0029153619
127. Griffiths P. D., Dobson B. R., Jones G. R., Clarke D. T., Iron in the basal ganglia in Parkinson's disease. An in vitro study using extended X-ray absorption fine structure and cryo-electron microscopy. Brain 1999 122 4 667 673 2-s2.0-0032898122 10.1093/brain/122.4.667 (Pubitemid 29158775)
128. Oakley A. E., Collingwood J. F., Dobson J., Love G., Perrott H. R., Edwardson J. A., Elstner M., Morris C. M., Individual dopaminergic neurons show raised iron levels in Parkinson disease. Neurology 2007 68 21 1820 1825 2-s2.0-34249034604 10.1212/01.wnl.0000262033.01945.9a (Pubitemid 46791395)
129. Popescu B. F. G., George M. J., Bergmann U., Garachtchenko A. V., Kelly M. E., McCrea R. P. E., Lüning K., Devon R. M., George G. N., Hanson A. D., Harder S. M., Chapman L. D., Pickering I. J., Nichol H., Mapping metals in Parkinson's and normal brain using rapid-scanning x-ray fluorescence. Physics in Medicine and Biology 2009 54 3 651 663 2-s2.0-63649144858 10.1088/0031-9155/54/ 3/012
130. Schweitzer K. J., Brüssel T., Leitner P., Krüger R., Bauer P., Woitalla D., Tomiuk J., Gasser T., Berg D., Transcranial ultrasound in different monogenetic subtypes of Parkinson's disease. Journal of Neurology 2007 254 5 613 616 2-s2.0-34249107672 10.1007/s00415-006-0369-7 (Pubitemid 46781971)
131. Hagenah J. M., König I. R., Becker B., Hilker R., Kasten M., Hedrich K., Pramstaller P. P., Klein C., Seidel G., Substantia nigra hyperechogenicity correlates with clinical status and number of Parkin mutated alleles. Journal of Neurology 2007 254 10 1407 1413 2-s2.0-36148995473 10.1007/s00415-007-0567-y (Pubitemid 350112333)
132. Hagenah J. M., Becker B., Brüggemann N., Djarmati A., Lohmann K., Sprenger A., Klein C., Seidel G., Transcranial sonography findings in a large family with homozygous and heterozygous PINK1 mutations. Journal of Neurology, Neurosurgery and Psychiatry 2008 79 9 1071 1074 2-s2.0-50449095891 10.1136/jnnp.2007.142174
133. Brüggemann N., Hagenah J., Stanley K., Klein C., Wang C., Raymond D., Ozelius L., Bressman S., Saunders-Pullman R., Substantia nigra hyperechogenicity with LRRK2 G2019S mutations. Movement Disorders 2011 26 5 885 888 2-s2.0-79955081027 10.1002/mds.23644
134. Shulman J. M., De Jager P. L., Feany M. B., Parkinson's disease: genetics and pathogenesis. Annual Review of Pathology 2011 6 193 222 2-s2.0-79751509762 10.1146/annurev-pathol-011110-130242