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NeuroMolecular Medicine
Published in: NeuroMolecular Medicine 4/2009

01-12-2009 | Original Paper

Interaction Between α-Synuclein and Metal Ions, Still Looking for a Role in the Pathogenesis of Parkinson’s Disease

Authors: Marco Bisaglia, Isabella Tessari, Stefano Mammi, Luigi Bubacco

Published in: NeuroMolecular Medicine | Issue 4/2009

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Abstract

The most recent literature on the interaction between α-synuclein in its several aggregation states and metal ions is discussed. This analysis shows two major types of interactions. Binding sites are present in the C-terminal region, and similar, low affinity (in the millimolar range) is exhibited toward many different metal ions, including copper and iron. A more complex scenario emerges for these latter metal ions, which are also able to coordinate with high affinity (in the micromolar range) to the N-terminal region of α-synuclein. Moreover, these redox-active metal ions may induce chemical modifications on the protein in vitro and in the reducing intracellular environment, and these modifications might be relevant for the aggregation properties of α-synuclein. Finally, an attempt is made to contextualize the interaction between α-synuclein and these metal ions in the framework of the elusive and multifactorial pathogenesis of Parkinson’s disease.
Literature
Abeliovich, A., Schmitz, Y., Farinas, I., Choi-Lundberg, D., Ho, W. H., Castillo, P. E., et al. (2000). Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron, 25, 239–252.CrossRefPubMed
Berg, D., Youdim, M. B., & Riederer, P. (2004). Redox imbalance. Cell and Tissue Research, 318, 201–213.CrossRefPubMed
Bertoncini, C. W., Jung, Y. S., Fernandez, C. O., Hoyer, W., Griesinger, C., Jovin, T. M., et al. (2005). Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein. Proceedings of the National Academy of Sciences of the United States of America, 102, 1430–1435.CrossRefPubMed
Bharathi, & Rao, K. S. (2007). Thermodynamics imprinting reveals differential binding of metals to alpha-synuclein: relevance to Parkinson’s disease. Biochemical and Biophysical Research Communications, 359, 115–120.
Binolfi, A., Lamberto, G. R., Duran, R., Quintanar, L., Bertoncini, C. W., Souza, J. M., et al. (2008). Site-specific interactions of Cu(II) with alpha and beta-synuclein: Bridging the molecular gap between metal binding and aggregation. Journal of the American Chemical Society, 130, 11801–11812.CrossRefPubMed
Binolfi, A., Rasia, R. M., Bertoncini, C. W., Ceolin, M., Zweckstetter, M., Griesinger, C., et al. (2006). Interaction of alpha-synuclein with divalent metal ions reveals key differences: A link between structure, binding specificity and fibrillation enhancement. Journal of the American Chemical Society, 128, 9893–9901.CrossRefPubMed
Bisaglia, M., Mammi, S., & Bubacco, L. (2008). Structural insights on physiological functions and pathological effects of {alpha}-synuclein. FASEB Journal, 23, 329–340.CrossRefPubMed
Bisaglia, M., Schievano, E., Caporale, A., Peggion, E., & Mammi, S. (2006). The 11-mer repeats of human alpha-synuclein in vesicle interactions and lipid composition discrimination: A cooperative role. Biopolymers, 84, 310–316.CrossRefPubMed
Bisaglia, M., Tessari, I., Pinato, L., Bellanda, M., Giraudo, S., Fasano, M., et al. (2005). A topological model of the interaction between alpha-synuclein and sodium dodecyl sulfate micelles. Biochemistry, 44, 329–339.CrossRefPubMed
Bodles, A. M., Guthrie, D. J., Greer, B., & Irvine, G. B. (2001). Identification of the region of non-Abeta component (NAC) of Alzheimer’s disease amyloid responsible for its aggregation and toxicity. Journal of Neurochemistry, 78, 384–395.CrossRefPubMed
Bortolus, M., Tombolato, F., Tessari, I., Bisaglia, M., Mammi, S., Bubacco, L., et al. (2008). Broken helix in vesicle and micelle-bound alpha-synuclein: Insights from site-directed spin labeling-EPR experiments and MD simulations. Journal of the American Chemical Society, 130, 6690–6691.CrossRefPubMed
Brown, D. R., Qin, K., Herms, J. W., Madlung, A., Manson, J., Strome, R., et al. (1997). The cellular prion protein binds copper in vivo. Nature, 390, 684–687.CrossRefPubMed
Cabin, D. E., Shimazu, K., Murphy, D., Cole, N. B., Gottschalk, W., McIlwain, K. L., et al. (2002). Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. Journal of Neuroscience, 22, 8797–8807.PubMed
Chartier-Harlin, M. C., Kachergus, J., Roumier, C., Mouroux, V., Douay, X., Lincoln, S., et al. (2004). Alpha-synuclein locus duplication as a cause of familial Parkinson’s disease. Lancet, 364, 1167–1169.CrossRefPubMed
Chen, M., Margittai, M., Chen, J., & Langen, R. (2007). Investigation of alpha-synuclein fibril structure by site-directed spin labeling. Journal of Biological Chemistry, 282, 24970–24979.CrossRefPubMed
Chinta, S. J., & Andersen, J. K. (2008). Redox imbalance in Parkinson’s disease. Biochimica et Biophysica Acta, 1780, 1362–1367.PubMed
Cole, N. B., Murphy, D. D., Lebowitz, J., Di Noto, L., Levine, R. L., & Nussbaum, R. L. (2005). Metal-catalyzed oxidation of alpha-synuclein: Helping to define the relationship between oligomers, protofibrils, and filaments. Journal of Biological Chemistry, 280, 9678–9690.CrossRefPubMed
Conway, K. A., Lee, S. J., Rochet, J. C., Ding, T. T., Williamson, R. E., & Lansbury, P. T., Jr. (2000). Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson’s disease: Implications for pathogenesis and therapy. Proceedings of the National Academy of Sciences of the United States of America, 97, 571–576.CrossRefPubMed
Davidson, W. S., Jonas, A., Clayton, D. F., & George, J. M. (1998). Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. Journal of Biological Chemistry, 273, 9443–9449.CrossRefPubMed
Dedmon, M. M., Lindorff-Larsen, K., Christodoulou, J., Vendruscolo, M., & Dobson, C. M. (2005). Mapping long-range interactions in alpha-synuclein using spin-label NMR and ensemble molecular dynamics simulations. Journal of the American Chemical Society, 127, 476–477.CrossRefPubMed
Der-Sarkissian, A., Jao, C. C., Chen, J., & Langen, R. (2003). Structural organization of alpha-synuclein fibrils studied by site-directed spin labeling. Journal of Biological Chemistry, 278, 37530–37535.CrossRefPubMed
Dexter, D. T., Carayon, A., Javoy-Agid, F., Agid, Y., Wells, F. R., Daniel, S. E., et al. (1991). Alterations in the levels of iron, ferritin and other trace metals in Parkinson’s disease and other neurodegenerative diseases affecting the basal ganglia. Brain, 114(Pt 4), 1953–1975.CrossRefPubMed
Dexter, D. T., Wells, F. R., Lees, A. J., Agid, F., Agid, Y., Jenner, P., et al. (1989). Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson’s disease. Journal of Neurochemistry, 52, 1830–1836.CrossRefPubMed
Ding, T. T., Lee, S. J., Rochet, J. C., & Lansbury, P. T., Jr. (2002). Annular alpha-synuclein protofibrils are produced when spherical protofibrils are incubated in solution or bound to brain-derived membranes. Biochemistry, 41, 10209–10217.CrossRefPubMed
Dorsey, E. R., Constantinescu, R., Thompson, J. P., Biglan, K. M., Holloway, R. G., Kieburtz, K., et al. (2007). Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology, 68, 384–386.CrossRefPubMed
Drew, S. C., Leong, S. L., Pham, C. L., Tew, D. J., Masters, C. L., Miles, L. A., et al. (2008). Cu2+ binding modes of recombinant alpha-synuclein—insights from EPR spectroscopy. Journal of the American Chemical Society, 130, 7766–7773.CrossRefPubMed
Eliezer, D., Kutluay, E., Bussell, R., Jr., & Browne, G. (2001). Conformational properties of alpha-synuclein in its free and lipid-associated states. Journal of Molecular Biology, 307, 1061–1073.CrossRefPubMed
Fink, A. L. (2006). The aggregation and fibrillation of alpha-synuclein. Accounts of Chemical Research, 39, 628–634.CrossRefPubMed
Fountaine, T. M., & Wade-Martins, R. (2007). RNA interference-mediated knockdown of alpha-synuclein protects human dopaminergic neuroblastoma cells from MPP(+) toxicity and reduces dopamine transport. Journal of Neuroscience Research, 85, 351–363.CrossRefPubMed
Friedlich, A. L., Tanzi, R. E., & Rogers, J. T. (2007). The 5′-untranslated region of Parkinson’s disease alpha-synuclein messenger RNA contains a predicted iron responsive element. Molecular Psychiatry, 12, 222–223.CrossRefPubMed
Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M. S., et al. (2002). Alpha-synuclein is phosphorylated in synucleinopathy lesions. Nature Cell Biology, 4, 160–164.CrossRefPubMed
Giasson, B. I., Duda, J. E., Murray, I. V., Chen, Q., Souza, J. M., Hurtig, H. I., et al. (2000). Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science, 290, 985–989.CrossRefPubMed
Giasson, B. I., Murray, I. V., Trojanowski, J. Q., & Lee, V. M. (2001). A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. Journal of Biological Chemistry, 276, 2380–2386.CrossRefPubMed
Glinka, Y., Tipton, K. F., & Youdim, M. B. (1996). Nature of inhibition of mitochondrial respiratory complex I by 6-Hydroxydopamine. Journal of Neurochemistry, 66, 2004–2010.PubMedCrossRef
Golts, N., Snyder, H., Frasier, M., Theisler, C., Choi, P., & Wolozin, B. (2002). Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein. Journal of Biological Chemistry, 277, 16116–16123.CrossRefPubMed
Heise, H., Hoyer, W., Becker, S., Andronesi, O. C., Riedel, D., & Baldus, M. (2005). Molecular-level secondary structure, polymorphism, and dynamics of full-length alpha-synuclein fibrils studied by solid-state NMR. Proceedings of the National Academy of Sciences of the United States of America, 102, 15871–15876.CrossRefPubMed
Hong, L., & Simon, J. D. (2009). Binding of Cu(II) to human alpha-synucleins: Comparison of wild type and the point mutations associated with the familial Parkinson’s disease. Journal of Physical Chemistry B, 113, 9551–9561.CrossRef
Hughes, A. J., Daniel, S. E., Ben-Shlomo, Y., & Lees, A. J. (2002). The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain, 125, 861–870.CrossRefPubMed
Inglis, K. J., Chereau, D., Brigham, E. F., Chiou, S. S., Schobel, S., Frigon, N. L., et al. (2009). Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system. Journal of Biological Chemistry, 284, 2598–2602.CrossRefPubMed
Iwai, A., Masliah, E., Yoshimoto, M., Ge, N., Flanagan, L., de Silva, H. A., et al. (1995). The precursor protein of non-A beta component of Alzheimer’s disease amyloid is a presynaptic protein of the central nervous system. Neuron, 14, 467–475.CrossRefPubMed
Kostka, M., Hogen, T., Danzer, K. M., Levin, J., Habeck, M., Wirth, A., et al. (2008). Single particle characterization of iron-induced pore-forming alpha-synuclein oligomers. Journal of Biological Chemistry, 283, 10992–11003.CrossRefPubMed
Kowalik-Jankowska, T., Rajewska, A., Jankowska, E., & Grzonka, Z. (2006a). Copper(II) binding by fragments of alpha-synuclein containing M1-D2- and -H50-residues: A combined potentiometric and spectroscopic study. Dalton Transactions, 5068–5076.
Kowalik-Jankowska, T., Rajewska, A., Jankowska, E., Wisniewska, K., & Grzonka, Z. (2006b). Products of Cu(II)-catalyzed oxidation of the N-terminal fragments of alpha-synuclein in the presence of hydrogen peroxide. Journal of Inorganic Biochemistry, 100, 1623–1631.CrossRefPubMed
Krantz, D. E., Peter, D., Liu, Y., & Edwards, R. H. (1997). Phosphorylation of a vesicular monoamine transporter by casein kinase II. Journal of Biological Chemistry, 272, 6752–6759.CrossRefPubMed
Kruger, R., Kuhn, W., Muller, T., Woitalla, D., Graeber, M., Kosel, S., et al. (1998). Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nature Genetics, 18, 106–108.CrossRefPubMed
Lai, B. C., Marion, S. A., Teschke, K., & Tsui, J. K. (2002). Occupational and environmental risk factors for Parkinson’s disease. Parkinsonism & Related Disorders, 8, 297–309.CrossRef
Larsen, K. E., Schmitz, Y., Troyer, M. D., Mosharov, E., Dietrich, P., Quazi, A. Z., et al. (2006). Alpha-synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis. Journal of Neuroscience, 26, 11915–11922.CrossRefPubMed
Lashuel, H. A., Hartley, D., Petre, B. M., Walz, T., & Lansbury, P. T., Jr. (2002). Neurodegenerative disease: Amyloid pores from pathogenic mutations. Nature, 418, 291.CrossRefPubMed
Lee, J. C., Gray, H. B., & Winkler, J. R. (2008). Copper(II) binding to alpha-synuclein, the Parkinson’s protein. Journal of the American Chemical Society, 130, 6898–6899.CrossRefPubMed
Lee, E. N., Lee, S. Y., Lee, D., Kim, J., & Paik, S. R. (2003). Lipid interaction of alpha-synuclein during the metal-catalyzed oxidation in the presence of Cu2+ and H2O2. Journal of Neurochemistry, 84, 1128–1142.CrossRefPubMed
Lee, F. J., Liu, F., Pristupa, Z. B., & Niznik, H. B. (2001). Direct binding and functional coupling of alpha-synuclein to the dopamine transporters accelerate dopamine-induced apoptosis. FASEB Journal, 15, 916–926.CrossRefPubMed
Lesage, S., & Brice, A. (2009). Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Human Molecular Genetics, 18, R48–R59.CrossRefPubMed
Li, W., West, N., Colla, E., Pletnikova, O., Troncoso, J. C., Marsh, L., et al. (2005). Aggregation promoting C-terminal truncation of alpha-synuclein is a normal cellular process and is enhanced by the familial Parkinson’s disease-linked mutations. Proceedings of the National Academy of Sciences of the United States of America, 102, 2162–2167.CrossRefPubMed
Liu, L. L., & Franz, K. J. (2007). Phosphorylation-dependent metal binding by alpha-synuclein peptide fragments. JBIC Journal of Biological Inorganic Chemistry, 12, 234–247.CrossRef
Lotharius, J., Barg, S., Wiekop, P., Lundberg, C., Raymon, H. K., & Brundin, P. (2002). Effect of mutant alpha-synuclein on dopamine homeostasis in a new human mesencephalic cell line. Journal of Biological Chemistry, 277, 38884–38894.CrossRefPubMed
Murphy, D. D., Rueter, S. M., Trojanowski, J. Q., & Lee, V. M. (2000). Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. Journal of Neuroscience, 20, 3214–3220.PubMed
Murray, I. V., Giasson, B. I., Quinn, S. M., Koppaka, V., Axelsen, P. H., Ischiropoulos, H., et al. (2003). Role of alpha-synuclein carboxy-terminus on fibril formation in vitro. Biochemistry, 42, 8530–8540.CrossRefPubMed
Nakajo, S., Shioda, S., Nakai, Y., & Nakaya, K. (1994). Localization of phosphoneuroprotein 14 (PNP 14) and its mRNA expression in rat brain determined by immunocytochemistry and in situ hybridization. Brain Research. Molecular Brain Research, 27, 81–86.CrossRefPubMed
Paik, S. R., Shin, H. J., & Lee, J. H. (2000). Metal-catalyzed oxidation of alpha-synuclein in the presence of Copper(II) and hydrogen peroxide. Archives of Biochemistry and Biophysics, 378, 269–277.CrossRefPubMed
Paik, S. R., Shin, H. J., Lee, J. H., Chang, C. S., & Kim, J. (1999). Copper(II)-induced self-oligomerization of alpha-synuclein. Biochemical Journal, 340(Pt 3), 821–828.CrossRefPubMed
Pall, H. S., Williams, A. C., Blake, D. R., Lunec, J., Gutteridge, J. M., Hall, M., et al. (1987). Raised cerebrospinal-fluid copper concentration in Parkinson’s disease. Lancet, 2, 238–241.CrossRefPubMed
Peng, J., Peng, L., Stevenson, F. F., Doctrow, S. R., & Andersen, J. K. (2007). Iron and paraquat as synergistic environmental risk factors in sporadic Parkinson’s disease accelerate age-related neurodegeneration. Journal of Neuroscience, 27, 6914–6922.CrossRefPubMed
Perez, R. G., Waymire, J. C., Lin, E., Liu, J. J., Guo, F., & Zigmond, M. J. (2002). A role for alpha-synuclein in the regulation of dopamine biosynthesis. Journal of Neuroscience, 22, 3090–3099.PubMed
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., et al. (1997). Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science, 276, 2045–2047.CrossRefPubMed
Ponka, P., Beaumont, C., & Richardson, D. R. (1998). Function and regulation of transferrin and ferritin. Seminars in Hematology, 35, 35–54.PubMed
Pronin, A. N., Morris, A. J., Surguchov, A., & Benovic, J. L. (2000). Synucleins are a novel class of substrates for G protein-coupled receptor kinases. Journal of Biological Chemistry, 275, 26515–26522.CrossRefPubMed
Rasia, R. M., Bertoncini, C. W., Marsh, D., Hoyer, W., Cherny, D., Zweckstetter, M., et al. (2005). Structural characterization of copper(II) binding to alpha-synuclein: Insights into the bioinorganic chemistry of Parkinson’s disease. Proceedings of the National Academy of Sciences of the United States of America, 102, 4294–4299.CrossRefPubMed
Riederer, P., Sofic, E., Rausch, W. D., Schmidt, B., Reynolds, G. P., Jellinger, K., et al. (1989). Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. Journal of Neurochemistry, 52, 515–520.CrossRefPubMed
Rochet, J. C., Conway, K. A., & Lansbury, P. T., Jr. (2000). Inhibition of fibrillization and accumulation of prefibrillar oligomers in mixtures of human and mouse alpha-synuclein. Biochemistry, 39, 10619–10626.CrossRefPubMed
Ross, C. A., & Poirier, M. A. (2005). Opinion: What is the role of protein aggregation in neurodegeneration? Nature Reviews. Molecular Cell Biology, 6, 891–898.CrossRefPubMed
Sandal, M., Valle, F., Tessari, I., Mammi, S., Bergantino, E., Musiani, F., et al. (2008). Conformational equilibria in monomeric alpha-synuclein at the single-molecule level. PLoS Biology, 6, e6.CrossRefPubMed
Segrest, J. P., Jones, M. K., De Loof, H., Brouillette, C. G., Venkatachalapathi, Y. V., & Anantharamaiah, G. M. (1992). The amphipathic helix in the exchangeable apolipoproteins: A review of secondary structure and function. Journal of Lipid Research, 33, 141–166.PubMed
Serpell, L. C., Berriman, J., Jakes, R., Goedert, M., & Crowther, R. A. (2000). Fiber diffraction of synthetic alpha-synuclein filaments shows amyloid-like cross-beta conformation. Proceedings of the National Academy of Sciences of the United States of America, 97, 4897–4902.CrossRefPubMed
Shults, C. W. (2006). Lewy bodies. Proceedings of the National Academy of Sciences of the United States of America, 103, 1661–1668.CrossRefPubMed
Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., et al. (2003). Alpha-synuclein locus triplication causes Parkinson’s disease. Science, 302, 841.CrossRefPubMed
Souza, J. M., Giasson, B. I., Chen, Q., Lee, V. M., & Ischiropoulos, H. (2000). Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies. Journal of Biological Chemistry, 275, 18344–18349.CrossRefPubMed
Spillantini, M. G., Schmidt, M. L., Lee, V. M., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997). Alpha-synuclein in Lewy bodies. Nature, 388, 839–840.CrossRefPubMed
Stokes, A. H., Hastings, T. G., & Vrana, K. E. (1999). Cytotoxic and genotoxic potential of dopamine. Journal of Neuroscience Research, 55, 659–665.CrossRefPubMed
Sung, Y. H., Rospigliosi, C., & Eliezer, D. (2006). NMR mapping of copper binding sites in alpha-synuclein. Biochimica et Biophysica Acta, 1764, 5–12.PubMed
Tehranian, R., Montoya, S. E., Van Laar, A. D., Hastings, T. G., & Perez, R. G. (2006). Alpha-synuclein inhibits aromatic amino acid decarboxylase activity in dopaminergic cells. Journal of Neurochemistry, 99, 1188–1196.CrossRefPubMed
Ulmer, T. S., Bax, A., Cole, N. B., & Nussbaum, R. L. (2005). Structure and dynamics of micelle-bound human alpha-synuclein. Journal of Biological Chemistry, 280, 9595–9603.CrossRefPubMed
Uversky, V. N. (2003). A protein-chameleon: Conformational plasticity of alpha-synuclein, a disordered protein involved in neurodegenerative disorders. Journal of Biomolecular Structure and Dynamics, 21, 211–234.PubMed
Uversky, V. N., Li, J., & Fink, A. L. (2001a). Evidence for a partially folded intermediate in alpha-synuclein fibril formation. Journal of Biological Chemistry, 276, 10737–10744.CrossRefPubMed
Uversky, V. N., Li, J., & Fink, A. L. (2001b). Metal-triggered structural transformations, aggregation, and fibrillation of human alpha-synuclein. A possible molecular NK between Parkinson’s disease and heavy metal exposure. Journal of Biological Chemistry, 276, 44284–44296.CrossRefPubMed
Uversky, V. N., Yamin, G., Munishkina, L. A., Karymov, M. A., Millett, I. S., Doniach, S., et al. (2005). Effects of nitration on the structure and aggregation of alpha-synuclein. Brain Research. Molecular Brain Research, 134, 84–102.CrossRefPubMed
Uversky, V. N., Yamin, G., Souillac, P. O., Goers, J., Glaser, C. B., & Fink, A. L. (2002). Methionine oxidation inhibits fibrillation of human alpha-synuclein in vitro. FEBS Letters, 517, 239–244.CrossRefPubMed
Vilar, M., Chou, H. T., Luhrs, T., Maji, S. K., Riek-Loher, D., Verel, R., et al. (2008). The fold of alpha-synuclein fibrils. Proceedings of the National Academy of Sciences of the United States of America, 105, 8637–8642.CrossRefPubMed
Volles, M. J., & Lansbury, P. T., Jr. (2002). Vesicle permeabilization by protofibrillar alpha-synuclein is sensitive to Parkinson’s disease-linked mutations and occurs by a pore-like mechanism. Biochemistry, 41, 4595–4602.CrossRefPubMed
Weinreb, P. H., Zhen, W., Poon, A. W., Conway, K. A., & Lansbury, P. T., Jr. (1996). NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry, 35, 13709–13715.CrossRefPubMed
Wersinger, C., Prou, D., Vernier, P., & Sidhu, A. (2003). Modulation of dopamine transporter function by alpha-synuclein is altered by impairment of cell adhesion and by induction of oxidative stress. FASEB Journal, 17, 2151–2153.PubMed
Wright, J. A., Wang, X., & Brown, D. R. (2009). Unique copper-induced oligomers mediate alpha-synuclein toxicity. FASEB Journal, 23, 4069–4076.CrossRef
Yamin, G., Glaser, C. B., Uversky, V. N., & Fink, A. L. (2003). Certain metals trigger fibrillation of methionine-oxidized alpha-synuclein. Journal of Biological Chemistry, 278, 27630–27635.CrossRefPubMed
Yavich, L., Tanila, H., Vepsalainen, S., & Jakala, P. (2004). Role of alpha-synuclein in presynaptic dopamine recruitment. Journal of Neuroscience, 24, 11165–11170.CrossRefPubMed
Youdim, M. B., Ben-Shachar, D., & Riederer, P. (1991). Iron in brain function and dysfunction with emphasis on Parkinson’s disease. European Neurology, 31(Suppl 1), 34–40.CrossRefPubMed
Yu, W. R., Jiang, H., Wang, J., & Xie, J. X. (2008). Copper (Cu2+) induces degeneration of dopaminergic neurons in the nigrostriatal system of rats. Neuroscience Bulletin, 24, 73–78.CrossRefPubMed
Zarranz, J. J., Alegre, J., Gomez-Esteban, J. C., Lezcano, E., Ros, R., Ampuero, I., et al. (2004). The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Annals of Neurology, 55, 164–173.CrossRefPubMed
Zecca, L., Stroppolo, A., Gatti, A., Tampellini, D., Toscani, M., Gallorini, M., et al. (2004). The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging. Proceedings of the National Academy of Sciences of the United States of America, 101, 9843–9848.CrossRefPubMed
Metadata
Title
Interaction Between α-Synuclein and Metal Ions, Still Looking for a Role in the Pathogenesis of Parkinson’s Disease
Authors
Marco Bisaglia
Isabella Tessari
Stefano Mammi
Luigi Bubacco
Publication date
01-12-2009
Publisher
Humana Press Inc
Published in
NeuroMolecular Medicine / Issue 4/2009
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-009-8082-1

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