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Is neuromelanin changed in Parkinson’s disease? Investigations by magnetic spectroscopies

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Summary.

Human mesencephalic neuromelanin (NM) is characterized by an irregular, undefined structure, making its characterization by usual physico-chemical methodologies quite difficult. NM isolated from controls and from Parkinson’s Disease (PD) patients was compared by high-resolution solid-state nuclear magnetic resonance (NMR). The pigment from PD patients appeared to be mainly composed of highly cross-linked, protease-resistant lipo-proteic material, with disappearance of melanin NMR resonances, suggesting melanin breakout due to oxidative stress conditions. Moreover, alpha-synuclein was detected in NM of PD patients and controls after cleavage of the melanin backbone under solubilizing conditions.

NM stores iron ions as oxyhydroxide iron clusters containing thousands of iron atoms. Electron Paramagnetic Resonance (EPR) investigations and magnetic susceptibility measurements confirmed the occurrence of magnetic coupling among iron atoms, whereas in synthetic melanin the occurrence of isolated Fe3+ ions was evident. NM from PD patients showed a lower total magnetization, possibly suggesting a progressive Fe migration from its storage environment (i.e., NM) to the cytosol.

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References

  • S Aime M Fasano B Bergamasco L Lopiano G Valente (1994) ArticleTitleEvidence for a glycidic-lipidic matrix in human neuromelanin, potentially responsible for the enhanced iron sequestering ability of substantia nigra J Neurochem 62 369–371 Occurrence Handle8263538 Occurrence Handle1:CAS:528:DyaK2cXltVOqsg%3D%3D Occurrence Handle10.1046/j.1471-4159.1994.62010369.x

    Article  PubMed  CAS  Google Scholar 

  • S Aime B Bergamasco D Biglino G Digilio M Fasano E Giamello L Lopiano (1997) ArticleTitleEPR investigations of the iron domain in neuromelanin Biochim Biophys Acta 1361 49–58 Occurrence Handle9247089 Occurrence Handle1:CAS:528:DyaK2sXjvVygu74%3D

    PubMed  CAS  Google Scholar 

  • S Aime B Bergamasco M Casu G Digilio M Fasano S Giraudo L Lopiano (2000) ArticleTitleIsolation and 13C-NMR characterization of an insoluble proteinaceous fraction from substantia nigra of Parkinson’s disease patients Mov Disord 15 977–981 Occurrence Handle11009208 Occurrence Handle1:STN:280:DC%2BD3cvlt1yhtQ%3D%3D Occurrence Handle10.1002/1531-8257(200009)15:5<977::AID-MDS1032>3.0.CO;2-Q

    Article  PubMed  CAS  Google Scholar 

  • S Aime M Fasano E Terreno CJ Groombridge (1991) ArticleTitleNMR studies of melanins: Characterization of a soluble Melanin Free Acid (MFA) from Sepia ink Pigm Cell Res 4 216–221 Occurrence Handle1:CAS:528:DyaK38XlsVOntrs%3D

    CAS  Google Scholar 

  • KJ Barnham CL Masters AI Bush (2004) ArticleTitleNeurodegenerative diseases and oxidative stress Nat Rev Drug Disc 3 205–214 Occurrence Handle1:CAS:528:DC%2BD2cXit12nsL4%3D Occurrence Handle10.1038/nrd1330

    Article  CAS  Google Scholar 

  • F Bolzoni S Giraudo L Lopiano B Bergamasco M Fasano PR Crippa (2002) ArticleTitleMagnetic investigation of human mesencephalic neuromelanin Biochim Biophys Acta 1586 210–218 Occurrence Handle11959462 Occurrence Handle1:CAS:528:DC%2BD38XivVSmtr8%3D

    PubMed  CAS  Google Scholar 

  • H Braak E Ghebremedhin U Rub H Bratzke K Del Tredici (2004) ArticleTitleStages in the development of Parkinson’s disease-related pathology Cell Tissue Res 318 121–134 Occurrence Handle15338272 Occurrence Handle10.1007/s00441-004-0956-9

    Article  PubMed  Google Scholar 

  • KA Conway JC Rochet RM Bieganski PT Lansbury SuffixJr (2001) ArticleTitleKinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct Science 294 1346–1349 Occurrence Handle11701929 Occurrence Handle1:CAS:528:DC%2BD3MXotlKmurk%3D Occurrence Handle10.1126/science.1063522

    Article  PubMed  CAS  Google Scholar 

  • K Double L Zecca P Costo M Mauer C Griesinger S Ito D Ben-Shachar G Bringmann RG Fariello P Riederer M Gerlach (2000) ArticleTitleStructural characteristics of human substantia nigra neuromelanin and synthetic dopamine melanins J Neurochem 75 2583–2589 Occurrence Handle11080212 Occurrence Handle1:CAS:528:DC%2BD3cXotFKntrc%3D Occurrence Handle10.1046/j.1471-4159.2000.0752583.x

    Article  PubMed  CAS  Google Scholar 

  • M Fasano S Giraudo S Coha B Bergamasco L Lopiano (2003) ArticleTitleResidual substantia nigra neuromelanin in Parkinson’s disease is cross-linked to alpha-synuclein Neurochem Int 42 603–606 Occurrence Handle12590943 Occurrence Handle1:CAS:528:DC%2BD3sXht1Cqsb8%3D Occurrence Handle10.1016/S0197-0186(02)00161-4

    Article  PubMed  CAS  Google Scholar 

  • H Fedorow F Tribl G Halliday M Gerlach P Riederer KL Double (2005) ArticleTitleNeuromelanin in human dopamine neurons: Comparison with peripheral melanins and relevance to Parkinson’s disease Progr Neurobiol 75 109–124 Occurrence Handle15784302 Occurrence Handle1:CAS:528:DC%2BD2MXisFKjsb8%3D Occurrence Handle10.1016/j.pneurobio.2005.02.001

    Article  PubMed  CAS  Google Scholar 

  • J Galazka-Friedman ER Bauminger A Friedman M Barcikowska D Hechel I Nowik (1996) ArticleTitleIron in parkinsonian and control substantia nigra – a Mössbauer spectroscopy study Mov Disord 11 8–16 Occurrence Handle8771061 Occurrence Handle1:STN:280:DyaK28zms12ntQ%3D%3D Occurrence Handle10.1002/mds.870110104

    Article  PubMed  CAS  Google Scholar 

  • J Galazka-Friedman ER Bauminger D Koziorowski A Friedman (2004) ArticleTitleMössbauer spectroscopy and ELISA studies reveal differences between Parkinson’s disease and control substantia nigra Biochim Biophys Acta 1688 130–136 Occurrence Handle14990343 Occurrence Handle1:CAS:528:DC%2BD2cXhsVKhsL8%3D

    PubMed  CAS  Google Scholar 

  • M Gerlach AX Trautwein L Zecca MB Youdim P Riederer (1995) ArticleTitleMössbauer spectroscopic studies of purified human neuromelanin isolated from the substantia nigra J Neurochem 65 923–926 Occurrence Handle7616255 Occurrence Handle1:CAS:528:DyaK2MXntFGgtL0%3D Occurrence Handle10.1046/j.1471-4159.1995.65020923.x

    Article  PubMed  CAS  Google Scholar 

  • L Lopiano M Chiesa G Digilio S Giraudo B Bergamasco E Torre M Fasano (2000a) ArticleTitleQ-band EPR investigations of neuromelanin in control and Parkinson’s disease patients Biochim Biophys Acta 1500 306–312 Occurrence Handle1:CAS:528:DC%2BD3cXhsVahsLc%3D

    CAS  Google Scholar 

  • L Lopiano M Fasano S Giraudo G Digilio B Bergamasco E Torre SH Koenig S Aime (2000b) ArticleTitleNuclear magnetic relaxation dispersion profiles of substantia nigra pars compacta in Parkinson’s disease patients are consistent with protein aggregation Neurochem Int 37 331–336 Occurrence Handle1:CAS:528:DC%2BD3cXmsVWltb4%3D Occurrence Handle10.1016/S0197-0186(00)00036-X

    Article  CAS  Google Scholar 

  • J Lotharius P Brundin (2002) ArticleTitleImpaired dopamine storage resulting from alpha-synuclein mutations may contribute to the pathogenesis of Parkinson’s disease Hum Mol Genet 11 2395–2407 Occurrence Handle12351575 Occurrence Handle1:CAS:528:DC%2BD38XnvVems7s%3D Occurrence Handle10.1093/hmg/11.20.2395

    Article  PubMed  CAS  Google Scholar 

  • L Zecca M Gallorini V Schunemann AX Trautwein M Gerlach P Riederer P Vezzoni D Tampellini (2001) ArticleTitleIron, neuromelanin and ferritin content in the substantia nigra of normal subjects at different ages: consequences for iron storage and neurodegenerative processes J Neurochem 76 1766–1773 Occurrence Handle11259494 Occurrence Handle1:CAS:528:DC%2BD3MXitlSkt74%3D Occurrence Handle10.1046/j.1471-4159.2001.00186.x

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Structural and Functional Biology, and Centre of Neuroscience, University of Insubria, Busto Arsizio, VA, Italy

    M. Fasano

  2. Department of Neuroscience, University of Torino, Torino, Italy

    B. Bergamasco & L. Lopiano

  3. Salvatore Maugeri Foundation, I.R.C.C.S., Pavia, Italy

    B. Bergamasco

Authors
  1. M. Fasano
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  2. B. Bergamasco
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  3. L. Lopiano
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Fasano, M., Bergamasco, B. & Lopiano, L. Is neuromelanin changed in Parkinson’s disease? Investigations by magnetic spectroscopies. J Neural Transm 113, 769–774 (2006). https://doi.org/10.1007/s00702-005-0448-4

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  • DOI: https://doi.org/10.1007/s00702-005-0448-4

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