Molecular Neurobiology

, Volume 31, Issue 1–3, pp 243–254 | Cite as

α-Synuclein and dopamine metabolism



α-Synuclein (α-Syn), a 140-amino-acid protein richly expressed in presynaptic terminals in the central nervous system, has been shown to play a central role in the pathogenesis of Parkinson’s disease. Although the normal functions of α-Syn remain elusive, accumulating evidence shows that the molecule is involved in multiple steps related to dopamine metabolism, including dopamine synthesis, storage, release, and uptake. The regulatory effect of α-Syn on dopamine metabolism is likely to tone down the amount of cytoplasmic dopamine at nerve terminals, thereby limiting its conversion to highly reactive oxidative molecules. Formation of α-Syn protofibrils triggered by factors such as gene mutations and environmental toxins can make the molecule lose its normal functions, leading to disrupted homeostasis of dopamine metabolism, increased cytoplasmic dopamine levels, and enhanced oxidative stress in dopaminergic neurons. The enhanced oxidative stress will, in turn, exacerbate the formation of α-Syn protofibrils and drive the neurons into a vicious cycle, which will finally result in the selective degeneration of the dopaminergic neurons associated with Parkinson’s disease.

Index Entries

Parkinson’s disease α-synuclein dopamine neuron oxidative stress 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Recchia A., Debetto P., Negro A., Guidolin D., Skaper S.D., and Giusti P. (2004) Alpha-synuclein and Parkinson’s disease. FASEB J. 18, 617–626.PubMedCrossRefGoogle Scholar
  2. 2.
    Polymeropoulos M.H., Lavedan C., Leroy E., et al. (1997) Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science 276, 2045–2047.PubMedCrossRefGoogle Scholar
  3. 3.
    Krüger R., Kuhn W., Muller T., et al. (1998) Ala30Pro mutation in the gene encoding α-Synuclein in Parkinson’s disease. Nat. Genet. 18, 106–108.PubMedCrossRefGoogle Scholar
  4. 4.
    Chan P., Tanner C.M., Jiang X., and Langston J.W. (1998) Failure to find the alpha-synuclein gene missense mutation (G209A) in 100 patients with younger onset Parkinson’s disease. Neurology 50, 513–514.PubMedGoogle Scholar
  5. 5.
    Chan P., Jiang X., Forno L.S., Di Monte D.A., Tanner C.M., and Langston J.W. (1998) Absence of mutations in the coding region of the alphasynuclein gene pathologically proven Parkinson’s disease. Neurology 50, 1136–1137.PubMedGoogle Scholar
  6. 6.
    Spillantini M.G., Schmidt M.L., Lee V.M., Trojanowski J.Q., Jakes R., and Goedert M. (1997) Alpha-synuclein in Lewy bodies. Nature (London) 388, 839–840.CrossRefGoogle Scholar
  7. 7.
    Spillantini M.G., Crowther R.A., Jakes R., Hasegawa M., and Goedert M. (1998) Alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. USA 95, 6469–6473.PubMedCrossRefGoogle Scholar
  8. 8.
    Baba M., Nakajo S., Tu P.H., et al. (1998) Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am. J. Pathol. 152, 879–884.PubMedGoogle Scholar
  9. 9.
    Takeda A., Mallory M., Sundsmo M., Honer W., Hansen L., and Masliah E. (1998) Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders. Am. J. Pathol. 152, 367–372.PubMedGoogle Scholar
  10. 10.
    Trojanowski J.Q. and Lee V.M.Y. (1998) Aggregation of neurofilament and alpha-synuclein proteins in Lewy bodies: implications for the pathogenesis of Parkinson disease and Lewy body dementia. Arch. Neurol. 55, 151–152.PubMedCrossRefGoogle Scholar
  11. 11.
    Arima K., Uéda K., Sunohara N., et al. (1998) Immunoelectron microscopic demonstration of NACP/alpha-synuclein epitopes on the filamentous component of Lewy bodies in Parkinson’s disease and in dementia with Lewy bodies. Brain Res. 808, 93–100.PubMedCrossRefGoogle Scholar
  12. 12.
    Masliah E., Rockenstein E., Veinbergs I., et al. (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 287, 1265–1269.PubMedCrossRefGoogle Scholar
  13. 13.
    Feany M.B. and Bender W.W. (2000) A drosophila model of Parkinson’s disease. Nature 404, 394–398.PubMedCrossRefGoogle Scholar
  14. 14.
    Conway K.A., Rochet J.C., Bieganski R.M., and Lansbury P.T., Jr. (2001) Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 294, 1346–1349.PubMedCrossRefGoogle Scholar
  15. 15.
    Lashuel H.A., Petre B.M., Wall J., et al. (2002) Alpha-synuclein, especially the Parkinson’s disease-associated mutants, forms pore-like annular and tubular protofibrils. J. Mol. Biol. 322, 1089–1102.PubMedCrossRefGoogle Scholar
  16. 16.
    Lee H.J. and Lee S.J. (2002) Characterization of cytoplasmic alpha-synuclein aggregates. Fibril formation is tightly linked to the inclusion-forming process in cells. J. Biol. Chem. 277, 48,976–48,983.Google Scholar
  17. 17.
    Narhi L., Wood S.J., Steavenson S., et al. (1999) Both familial Parkinson’s disease mutations accelerate alpha-synuclein aggregation. J. Biol. Chem. 274, 9843–9846.PubMedCrossRefGoogle Scholar
  18. 18.
    Clayton D.F. and George J.M. (1998) The synucleins: a family of proteins involved in synaptic function, plasticity, neurodegeneration and disease. Trends Neurosci. 21, 249–254.PubMedCrossRefGoogle Scholar
  19. 19.
    Lavedan C. (1998) The synuclein family. Genome Res. 8, 871–880.PubMedGoogle Scholar
  20. 20.
    Lucking C.B. and Brice A. (2000) Alpha-synuclein and Parkinson’s disease. Cell Mol. Life Sci. 57, 1894–1908.PubMedCrossRefGoogle Scholar
  21. 21.
    Kahle P.J., Neumann M., Ozman L., and Haass, C. (2000) Physiology and pathophysiology of alpha-synuclein: cell culture and transgenic animal models based on a Parkinson’s disease-associated protein. Ann. NY Acad. Sci. 920, 33–41.PubMedCrossRefGoogle Scholar
  22. 22.
    Conway K.A., Lee S.J., Rochet J.C., Ding T.T., Williamson R.E., and Lansbury P.T., Jr. (2000) Acceleration of oligomerization, not fibrillization, is a shared property of both alphasynuclein mutations linked to early-onset Parkinson’s disease: implications for pathogenesis and therapy. Proc. Natl. Acad. Sci. USA 97, 571–576.PubMedCrossRefGoogle Scholar
  23. 23.
    El-Agnaf O.M. and Irvine G.B. (2000) Formation and properties of amyloid-like fibrils derived from alphasynuclein and related proteins. J. Struct. Biol. 130, 300–309.PubMedCrossRefGoogle Scholar
  24. 24.
    Ma Q.L., Chan P., Yoshii M., and Uéda K. (2003) Alpha-synuclein aggregation and neurodegenerative diseases. J. Alzheimer’s Dis. 5, 139–148.Google Scholar
  25. 25.
    Mouradian M.M. (2002) Recent advances in the genetics and pathogenesis of Parkinson disease. Neurology 58, 179–185.PubMedGoogle Scholar
  26. 26.
    Zhou W., Schaack J., Zawada W.M., and Freed C.R. (2002) Overexpression of human alphasynuclein causes dopamine neuron death in primary human mesencephalic culture. Brain Res. 926, 42–50.PubMedCrossRefGoogle Scholar
  27. 27.
    Xu J., Kao S.-Y., Lee F.J.S., Song W., Jin L.-W., and Yankner B.A. (2002) Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat. Med. 8, 600–606.PubMedCrossRefGoogle Scholar
  28. 28.
    Maker H.S., Weiss C., Silides D.J., and Cohen G. (1981) Coupling of dopamine oxidation (monoamine oxidase activity) to glutathione oxidation via the generation of hydrogen peroxide in rat brain homogenates. J. Neurochem. 36, 589–593.PubMedCrossRefGoogle Scholar
  29. 29.
    Youdim M.B. (2003) What have we learnt from cDNA microarray gene expression studies about the role of iron in MPTP induced neurodegeneration and Parkinson’s disease? J. Neural Transm. 65(Suppl.), 73–88.Google Scholar
  30. 30.
    Graham D.G. (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinines. Mol. Pharmacol. 14, 633–643.PubMedGoogle Scholar
  31. 31.
    George J.M. (2002) The synucleins. Genome Biol. 3, 1–6.Google Scholar
  32. 32.
    Maroteaux L., Campanelli J.T., and Scheller R.H. (1988) Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J. Neurosci. 8, 2804–2815.PubMedGoogle Scholar
  33. 33.
    Uëda K., Fukushima H., Masliah E., et al. (1993) Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 11,282–11,286.CrossRefGoogle Scholar
  34. 34.
    Clayton D.F. and George J.M. (1999) Synucleins in synaptic plasticity and neurodegenerative disorders. J. Neurosci. Res. 58, 120–129.PubMedCrossRefGoogle Scholar
  35. 35.
    Perrin R.J., Woods W.S., Clayton D.F., and George J.M. (2000) Interaction of human alpha-synuclein and Parkinson’s disease variants with phospholipids. J. Biol. Chem. 275, 34,393–34,398.CrossRefGoogle Scholar
  36. 36.
    Du H.N., Tang L., Luo X.Y., et al. (2003) A peptide motif consisting of glycine, alanine, and valine is required for the fibrillization and cytotoxicity of human alpha-synuclein. Biochemistry 42, 8870–8878.PubMedCrossRefGoogle Scholar
  37. 37.
    Iwai A., Masliah E., Yoshimoto M., et al. (1995) The precursor protein of non-Aβ component of Alzheimer’s disease amyloid is a presynaptic protein of the central nervous system. Neuron 14, 467–475.PubMedCrossRefGoogle Scholar
  38. 38.
    Mori F., Tanji K., Yoshimoto M., Takahashi H., and Wakabayashi K. (2002) Immunohistochemical comparison of alpha- and beta-synuclein in adult rat central nervous system. Brain Res. 941, 118–126.PubMedCrossRefGoogle Scholar
  39. 39.
    Kahle P.J., Neumann M., Ozman L., et al. (2000) Subcellular localization of wild-type and Parkinson’s disease-associated mutant alpha-synuclein in human and transgenic mouse brain. J. Neurosci. 20, 6365–6373.PubMedGoogle Scholar
  40. 40.
    Sharon R., Goldberg M.S., Bar-Josef I., Betensky R.A., Shen J., and Selkoe D.J. (2001) Alpha-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins. Proc. Natl. Acad. Sci. USA 98, 9110–9115.PubMedCrossRefGoogle Scholar
  41. 41.
    Irizarry M.C., Kim T.W., McNamara M., et al. (1996) Characterisation of the precursor of the non-Aβ component of senile plaques (NACP) in the human central nervous system. J. Neuropathol. Exp. Neurol. 55, 889–895.PubMedGoogle Scholar
  42. 42.
    Galvin J.E., Schuck T.M., Lee V.M., and Trojanowski J.Q. (2001) Differential expression and distribution of alpha-, beta-, and gamma-synuclein in the developing human substantia nigra. Exp. Neurol. 168, 347–355.PubMedCrossRefGoogle Scholar
  43. 43.
    Jakowec M.W., Donaldson D.M., Barba J., and Petzinger G.M. (2001) Postnatal expression of alpha-synuclein protein in rodent substantia nigra and striatum. Dev. Neurosci. 23, 91–99.PubMedCrossRefGoogle Scholar
  44. 44.
    Li J.Y., Jensen H.P., and Dahlstrom A. (2002) Differential localization of alpha-, beta- and gamma-synucleins in the rat CNS. Neuroscience 113, 463–478.PubMedCrossRefGoogle Scholar
  45. 45.
    Davidson W.S., Jonas A., Clayton D.F., and George J.M. (1998) Stabilization of alpha-synuclein secondary structure upon binding to synthetic membrane. J. Biol. Chem. 273, 9443–9449.PubMedCrossRefGoogle Scholar
  46. 46.
    Murphy D.D., Rueter S.M., Trojanovski J.Q., and Lee V.M.-Y. (2000) Synucleins are developmentally expressed, and α-Synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons. J. Neurosci. 20, 3214–3220.PubMedGoogle Scholar
  47. 47.
    Ostrerova N., Petrucelli L., Farrer M., et al. (1999) Alpha-Synuclein shares physical and functional homology with 14-3-3 proteins. J. Neurosci. 19, 5782–5791.PubMedGoogle Scholar
  48. 48.
    Kim T.D., Paik S.R., Yang C.H., and Kim J. (2000) Structural changes in alpha-synuclein affect its chaperone-like activity in vitro. Protein Sci. 9, 2489–2496.PubMedCrossRefGoogle Scholar
  49. 49.
    Baptista M.J., O’Farrell C., Daya S., et al. (2003) Co-ordinate transcriptional regulation of dopamine synthesis genes by α-Synuclein in human neuroblastoma cell lines. J. Neurochem. 85, 957–968.PubMedCrossRefGoogle Scholar
  50. 50.
    Goers J., Manning-Bog A.B., McCormack A.L., et al. (2003) Nuclear localization of α-Synuclein and its interaction with histones. Biochemistry 42, 8465–8471.PubMedCrossRefGoogle Scholar
  51. 51.
    Cabin D.E., Shimazu K., Murphy D., et al. (2002) Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein. J. Neurosci. 22, 8797–8807.PubMedGoogle Scholar
  52. 52.
    Lotharius J., Barg S., Wiekop P., Lundberg C., Raymon H.K., and Brundin P. (2002) Effect of mutant alpha-synuclein on dopamine home-ostasis in a new human mesencephalic cell line. J. Biol. Chem. 277, 38,884–38,894.CrossRefGoogle Scholar
  53. 53.
    Lotharius J. and Brundin P. (2002) Impaired dopamine storage resulting from alpha-synuclein mutations may contribute to the pathogenesis of Parkinson’s disease. Hum. Mol. Genet. 11, 2395–2407.PubMedCrossRefGoogle Scholar
  54. 54.
    Lotharius J. and Brundin P. (2002) Pathogenesis of Parkinson’s disease: dopamine, vesicles and alpha-synuclein. Nat. Rev. Neurosci. 3, 932–942.PubMedCrossRefGoogle Scholar
  55. 55.
    Jenco J.M., Rawlingson A., Daniels B., and Morris A.J. (1998) Regulation of phospholipase D2: selective inhibition of mammalian phospholipase D isoenzymes by α- and β-synucleins. Biochemistry 37, 4901–4909.PubMedCrossRefGoogle Scholar
  56. 56.
    Ahn B.H., Rhim H., Kim S.Y., et al. (2002) α-Synuclein interacts with phospholipase D isozymes and inhibits pervandate induced phospholipase D activation in human embryonic kidney 293 cells. J. Biol. Chem. 277, 12,334–12,342.Google Scholar
  57. 57.
    Okochi M., Walter J., Koyama A., et al. (2000) Constitutive phosphorylation of the Parkinson’s disease associated alpha-synuclein. J. Biol. Chem. 275, 390–397.PubMedCrossRefGoogle Scholar
  58. 58.
    Jensen P.H., Hojrup P., Hager H., et al. (1999) Alpha-synuclein binds to T and stimulates the protein kinase A-catalysed τ phosphorylation of serine residues 262 and 356. J. Biol. Chem. 274, 25,481–25,489.Google Scholar
  59. 59.
    Pronin A.N., Morris A.J., Surguchov A., and Benovic J.L. (2000) Synucleins are a novel class of substrates for G protein-coupled receptor kinases. J. Biol. Chem. 275, 26,515–26,522.CrossRefGoogle Scholar
  60. 60.
    Ellis C.E., Schwartzberg P.L., Grider T.L., Fink D.W., and Nussbaum R.L. (2001) Alpha-synuclein is phosphorylated by members of the Src family of protein-tyrosine kinases. J. Biol. Chem. 276, 3879–3884.PubMedCrossRefGoogle Scholar
  61. 61.
    Nakamura T., Yamashita H., Nagano Y., et al. (2002) Activation of Pyk2/RAFTK induces tyrosine phosphorylation of alpha-synuclein via Src-family kinases. FEBS Lett. 521, 190–194.PubMedCrossRefGoogle Scholar
  62. 62.
    Schmidt A., Wolde M., Thiele C., et al. (1999) Endophilin I mediates synaptic vesicle formation by transfer arachidonate to lysophosphatidic acid. Nature (London) 401, 133–141.CrossRefGoogle Scholar
  63. 63.
    Heuser J.E. and Reese T.S. (1973) Evidence for recycling of synaptic vesicle membrane during transmitter release at the frog neuromuscular junction. J. Cell Biol. 57, 315–344.PubMedCrossRefGoogle Scholar
  64. 64.
    Lucking C.B. and Brice A. (2000) Alpha-synuclein and Parkinson’s disease. Cell. Mol. Life Sci. 57, 1894–908.PubMedCrossRefGoogle Scholar
  65. 65.
    Alim M.A., Hossain M.S., Arima K., et al. (2002) Tubulin seeds alpha-synuclein fibril formation. J. Biol. Chem. 277, 2112–2117.PubMedCrossRefGoogle Scholar
  66. 66.
    Jensen P.H., Islam K., Kenney J., Nielsen M.S., Power J., and Gai W.P. (2000) Microtubule-associated protein 1B is a component of cortical Lewy bodies and binds alpha-synuclein filaments. J. Biol. Chem. 275, 21,500–21,507.Google Scholar
  67. 67.
    D’Andrea M.R., Ilyin S., and Plata-Salaman C.R. (2001) Abnormal patterns of microtubule-associated protein-2 (MAP-2) immunolabeling in neuronal nuclei and Lewy bodies in Parkinson’s disease substantia nigra brain tissues. Neurosci. Lett. 306, 137–142.PubMedCrossRefGoogle Scholar
  68. 68.
    Engelender S., Kaminsky Z., Guo X., et al. (1999) Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions. Nat. Genet. 22, 110–114.PubMedCrossRefGoogle Scholar
  69. 69.
    Sharma N., Hewett J., Ozelius L.J., et al. (2001) A close association of torsin A and alpha-synuclein in Lewy bodies: a fluorescence resonance energy transfer study. Am. J. Pathol. 159, 339–344.PubMedGoogle Scholar
  70. 70.
    Sidhu A., Wersinger C., and Vernier P. (2004) Alpha-Synuclein regulation of the dopaminergic transporter: a possible role in the pathogenesis of Parkinson’s disease. FEBS Lett. 565(1–3), 1–5.PubMedCrossRefGoogle Scholar
  71. 71.
    Wersinger C., Prou D., Vernier P., Niznik H.B., and Sidhu A. (2003) Mutations in the lipid-binding domain of alpha-synuclein confer overlapping, yet distinct, functional properties in the regulation of dopamine transporter activity. Mol. Cell. Neurosci. 24(1), 91–105.PubMedCrossRefGoogle Scholar
  72. 72.
    Wersinger C., Vernier P., and Sidhu A. (2004) Trypsin disrupts the trafficking of the human dopamine transporter by alpha-synuclein and its A30P mutant. Biochemistry 43(5), 1242–1253.PubMedCrossRefGoogle Scholar
  73. 73.
    Wersinger C. and Sidhu A. (2003) Attenuation of dopamine transporter activity by alpha-synuclein. Neurosci Lett. 340(3), 189–192.PubMedCrossRefGoogle Scholar
  74. 74.
    Wersinger C., Prou D., Vernier P., and 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 J. E-pub. (14), 2151–2153.Google Scholar
  75. 75.
    Perez R.G., Waymire J.C., Lin E., Liu J.J., Guo F., and Zigmond M.J. (2002) A role for α-synuclein in the regulation of dopamine biosynthesis. J. Neurosci. 22, 3090–3099.PubMedGoogle Scholar
  76. 76.
    Kumer S.C. and Vrana K.E. (1996) Intricate regulation of tyrosine hydroxylase activity and gene expression. J. Neurochem. 67, 443–462.PubMedCrossRefGoogle Scholar
  77. 77.
    Ichimura T., Isobe T., Okuyama T., Yamauchi T., and Fujisawa H. (1987) Brain 14-3-3 protein is an activator protein that activates tryptophan 5-monooxygenase and tyrosine 3-monooxygenase in the presence of Ca2+ calmodulin-dependent protein kinase II. FEBS Lett. 219, 79–82.PubMedCrossRefGoogle Scholar
  78. 78.
    Ichimura T., Isobe T., Okuyama T., et al. (1988) Molecular cloning of cDNA coding for brain-specific 14-3-3 protein, a protein kinase-dependent activator of tyrosine and tryptophan hydroxylases. Proc. Natl. Acad. Sci. USA 85, 7084–7088.PubMedCrossRefGoogle Scholar
  79. 79.
    Toska K., Kleppe R., Armstrong C.G., Morrice N.A., Cohen P., and Haavik J. (2002) Regulation of tyrosine hydroxylase by stress-activated protein kinases. J. Neurochem. 83, 775–783.PubMedCrossRefGoogle Scholar
  80. 80.
    Sakurada K., Ohshima-Sakurada M., Palmer T.D., and Gage F.H. (1999) Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain. Development 126, 4017–4026.PubMedGoogle Scholar
  81. 81.
    Yu S., Zuo X.H., Li Y.H., et al. (2004) Inhibition of tyrosine hydroxylase expression in α-synuclein-transfected dopaminergic neuronal cells. Neurosci. Lett. 367, 34–39.PubMedCrossRefGoogle Scholar
  82. 82.
    Moussa C.E., Wersinger C., Tomita Y., and Sidhu A. (2004) Differential cytotoxicity of human wild type and mutant alpha-Synuclein in human neuroblastoma SH-SY5Y cells in the presence of dopamine. Biochemistry 43(18), 5539–5550.PubMedCrossRefGoogle Scholar
  83. 83.
    Giasson B.I. and Lee V.M. (2003) Are ubiquitination pathways central to Parkinson’s disease? Cell 114, 1–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Lansbury P.T. Jr. and Brice A. (2002) Genetics of Parkinson’s disease and biochemical studies of implicated gene products. Curr. Opin. Genet Dev. 12, 299–306.PubMedCrossRefGoogle Scholar
  85. 85.
    Giasson B.I., Duda J.E., Quinn S.M., Zhang B., Trojanowski J.Q., and Lee V.M. (2002) Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34, 521–533.PubMedCrossRefGoogle Scholar
  86. 86.
    Richfield E.K., Thiruchelvam M.J., Cory-Slechta D.A., et al. (2002) Behavioral and neurochemical effects of wild-type and mutated human alpha-synuclein in transgenic mice. Exp. Neurol. 175, 35–48.PubMedCrossRefGoogle Scholar
  87. 87.
    Vila M., Vukosavic S., Jackson-Lewis V., Neystat M., Jakowec M., and Przedborski S. (2000) Alpha-synuclein up-regulation in substantia nigra dopaminergic neurons following administration of the parkinsonian toxin MPTP. J. Neurochem. 74, 721–729.PubMedCrossRefGoogle Scholar
  88. 88.
    Sherer T.B., Kim J.H., Betarbet R., and Greenamyre J.T. (2003) Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp Neurol. 179(1), 9–16.PubMedCrossRefGoogle Scholar
  89. 89.
    Barja G. (2000) The flux of free radical attack through mitochondrial DNA is related to aging rate. Aging Clin. Exp. Res. 12, 342–355.Google Scholar
  90. 90.
    Giasson B.I., Duda J.E., Murray I.V., et al. (2000) Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 290, 985–989.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2005

Authors and Affiliations

  1. 1.Department of Neurobiology and the Sino-Japan Joint Laboratory on Neurodegenerative Diseases, Beijing Institute of GeriatricsXuanwu Hospital of Capital University of Medical SciencesBeijingChina
  2. 2.Institute for Hypoxia MedicineCapital University of Medical ScienceBeijingChina
  3. 3.Department of Neural PlasticityTokyo Institute of PsychiatryTokyoJapan

Personalised recommendations