Parkinson’s disease — a multifactorial neurodegenerative disorder

  • Olaf Riess
  • R. Krüger
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 56)


The pathogenesis of idiopathic Parkinson’s disease (PD) is not known, but is thought to be multifactorial, deriving from environmental factors acting on genetically predisposed individuals with aging. Association studies of DNA polymorphisms are able to detect a genetic background predisposing to PD. Mechanisms as oxidative stress, xenobiotica toxicity and altered dopamine metabolism might lead to a selective cell death of most vulnerable nerve cells and represent the primary subject to be studied by DNA analysis. Furthermore, protein aggregation is likely to be a major cause for the disease. Recently it has been shown that α-synuclein is accumulated in Lewy bodies of sporadic PD and mutated in some rare families with an autosomal dominant trait of the disease (ADPD). The identification of further genes responsible for PD will subsequently lead to first insights into the pathogenesis of one of the most common neurodegenerative disorders in humans.


Tyrosine Hydroxylase Alzheimer Disease Multiple System Atrophy Lewy Body Dementia With Lewy Body 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Balk J-H, Picetti R, Salardi A, Thiriet G, Dierich A, Depauis A, Le Meur M, Borrelli E (1995) Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors. Nature 377: 424–428CrossRefGoogle Scholar
  2. Bandmann O, Vaughan J, Holmans P, Marsden CD, Wood NW (1997) Association of slow acetylator genotype for N-acetyltransferase 2 with familial Parkinson’s disease. Lancet 350: 1136–1139PubMedCrossRefGoogle Scholar
  3. Burn DJ, Mark MH, Playford ED, et al (1992) Parkinson’s disease in twins studied with 18F-Dopa and positron emission tomography. Neurology 42: 1894–1900PubMedCrossRefGoogle Scholar
  4. Chinaglia G, Probst A, Palacios JM (1990) Neurotensin receptors in Parkinson’s disease and progressive supranuclear palsy: an autoradiografic study in basal ganglia. Neuroscience 39(2): 351–360PubMedCrossRefGoogle Scholar
  5. Costa P, Chekoway H, Levy D, Smith-Weller T, Franklin GM, Swanson PD, Costa LG (1997) Association of a polymorphism in intron 13 of the monoamine oxidase B gene with Parkinson disease. Am J Med Gen 74: 154–156CrossRefGoogle Scholar
  6. Frim DM, Uhler TA, Galpern WR, Beal MF, Breakefield XO, Isacson O (1994) Implanted fibroblasts genetically engineered to produce brain-derived neurotrophic factor prevent 1-methyl-4-phenylpyridinium toxicity to dopaminergic neurons in the rat. Proc Natl Acad Sci USA 91: 5104–5108PubMedCrossRefGoogle Scholar
  7. Gasser T, Wszolek ZK, Trofatter J, Ozelius L, Uitti RJ, Lee CS, Gusella J, Pfeiffer RF, Calne DB, Breakfield XO (1994) Genetic linkage studies in autosomal dominant Parkinsonism: evaluation of seven candidate genes. Ann Neurol 36: 387–396PubMedCrossRefGoogle Scholar
  8. Gasser T, Müller-Myhsok B, Wszolek ZK, et al (1997) Genetic complexity and Parkinson’s disease. Science 277: 388–389PubMedGoogle Scholar
  9. Golbe LI, Di Iorio G, Bonavita V, Miller DC, Duvoisin RC (1990) A large kindred with adPD. Ann Neurol 27: 276–282PubMedCrossRefGoogle Scholar
  10. Golbe LI (1993) A large kindred with PD: onset age, segregation ratios, and anticipation. Mov Disord 8: 406Google Scholar
  11. Harrington KA, Augood SJ, Kingsbury AE, Foster OJ, Emson PC (1996) Dopamine transporter (DAT) and synaptic vesicle amine transporter (VMAT2) gene expression in the substantia nigra of control and Parkinson’s disease. Mol Brain Res 36(1): 157–162PubMedCrossRefGoogle Scholar
  12. Heikkila RE, Kindt MV, Sonsalla PK (1988) Importance of monoamine oxidase A in the bioactivation of neurotoxic analogs of 1-methyl-4-phenyl-11,2,5,6-tetrahydropyridine. Proc Natl Acad Sci USA 85: 6172–6176PubMedCrossRefGoogle Scholar
  13. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinicopathologic study of 100 cases. J Neurol Neurosurg Psychiatry 55: 181–184PubMedCrossRefGoogle Scholar
  14. Hughes AJ, Daniel SE, Blankson S, Lees AJ (1993) A clinicopathologic study of 100 cases of Parkinson’s disease. Arch Neurol 50: 140–148PubMedCrossRefGoogle Scholar
  15. Hyman C, Hofer M, Barde YA (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350: 230–232PubMedCrossRefGoogle Scholar
  16. Javoy-Agid G, Hirsch EC, Dumas S (1990) Decreased tyrosine hydroxylase messenger RNA in the surviving dopamine neurons of the substantioa nigra in Parkinson’s disease: an in situ hybridization study. Neuroscience 38: 245–253PubMedCrossRefGoogle Scholar
  17. Jellinger KA (1993) Pathogenese und Pathophysiologie der Parkinson-Krankheit. Neuropsychiatrie 7(1): 29–37Google Scholar
  18. Jenner P, Schapira AHV, Marsden CD (1992) New insights into the cause of Parkinson’s disease. Neurology 42: 2241–2250PubMedCrossRefGoogle Scholar
  19. Kimpara T, Takeda A, Watanabe K, Itoyama Y, Ikawa S, Watanabe M, Arai H, Sasaki H, Higuchi S, Okita N, Takase S, Saito H, Takahashi K, Shibahara S (1997) Microsatellite polymorphism in the human heme oxygenase-1 promoter and its application in association studies with Alzheimer and Parkinson disease. Hum Genet 100: 145–147PubMedCrossRefGoogle Scholar
  20. Kish SJ, Rajput A, Gilbert J, Rozdilsky B, Chang LJ, Shannak K, Hornykiewicz O (1986) Elevated gamma-aminobutyric acid level in striatal but not extrastriatal brain regions in Parkinson’s disease: correlation with striatal dopamine loss. Ann Neurol 20(1): 26–31PubMedCrossRefGoogle Scholar
  21. Kitayama S, Wang J-B, Uhl GR (1993) Deopamine transporter mutants selectively increase MPP+ transport. Synapse 15: 58–62PubMedCrossRefGoogle Scholar
  22. Krüger R, Kuhn W, Müller Th, Woitalla D, Graeber M, Kösel S, Przuntek H, Epplen JT, Schöls L, Riess O (1998) Ala30Pro mutation in the gene encoding α-synuclein in Parkinson’s disease. Nat Genet 18: 106–108PubMedCrossRefGoogle Scholar
  23. Kurth JH, Kurth MC, Poduloso SE, Schwankhaus JD (1993) Association of a monoamine oxidase B allele with Parkinson’s disease. Ann Neurol 33: 368–372PubMedCrossRefGoogle Scholar
  24. Kurth JH, Eggers-Sedlet B, Liebermann A, Kurth MC (1997) Mov Disord 12(5): 835Google Scholar
  25. Langston JW, Irwin I, Langston EB, Forno LS (1984) Pargyline prevents MPTP induced parkinsonism in primates. Science 225: 1480–1482PubMedCrossRefGoogle Scholar
  26. LeCouteur DG, Leighton PW, McCann SJ, Pond SM (1997) Association of a polymorphism in the dopamine-transporter gene with Parkinson’s disease. Mov Disord 12: 760–763CrossRefGoogle Scholar
  27. Nishino N, Fujiwara H, Nogushi-Kuno SA, Tanaka C (1988) GABAA receptor but not muscarinic receptor density was decreased in the brain of patients with Parkinson’s disease. Jpn J Pharmacol 48(3): 331–339PubMedCrossRefGoogle Scholar
  28. Planté-Bordeneuve V, Davis MB, Maraganore DM, Marsden CD, Harding AE (1994) Tyrosine hydroxylase polymorphism in familial an sporadic Parkinson’s disease. Mov Disord 9: 337–339PubMedCrossRefGoogle Scholar
  29. Planté-Bordeneuve V, Taussig B, Thomas F, Said G, Wood NW, Marsden CD, Harding AE (1997) Evaluation of four candidate genes encoding proteins of the dopamine pathway in familial and sporadic Parkinson’s disease. Neurology 48: 1589–1593PubMedCrossRefGoogle Scholar
  30. Polymeropoulos M, Lavedan C, Leroy E, et al (1997) Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science 276: 2045–2047PubMedCrossRefGoogle Scholar
  31. Riederer P, Konradi C, Hebenstreit G, Youdim MB (1989) Neurochemical perspectives to the function of monoamine oxidase. Acta Neurol Scand [Suppl] 126: 41–45CrossRefGoogle Scholar
  32. Schellenberg GD (1995) Genetic dissection of Alzheimer disease, a heterogeneous disorder. Proc Natl Acad Sci USA 92: 8552–8559PubMedCrossRefGoogle Scholar
  33. Schmidt ML, Martin JA, Lee VMY, Trojanowski JQ (1996) Convergence of Lewy bodies and neurofibrillary tangles in amygdala neurons of Alzheimer’s disease and Lewy body disorders. Acta Neuropathol 91: 475–481PubMedCrossRefGoogle Scholar
  34. Scott WK, Stajich JM, Yamaoka LH, Speer MC, Vance JM, Roses AD, Pericak-Vance MA, The Deane Laboratory Parkinson Disease Research Group (1997) Genetic complexity and Parkinson’s disease. Science 277: 387–388PubMedCrossRefGoogle Scholar
  35. Seeman P, Van Tol HMM (1994) Dopamine receptor pharmacology. TIPS 15: 264–270PubMedGoogle Scholar
  36. Seidler A, Hellenbrand W, Robra B-P, Vieregge P, Nischan P, Joerg J, Oertel WH, Ulm G, Schneider E (1996) Possible environmental, occupational and other ecological factors for Parkinson’s disease: a case control study in Germany. Neurology 46: 1275–1284PubMedCrossRefGoogle Scholar
  37. Spillantini MG, Schmidt ML, Lee VM-Y, Jakes R, Goedert M (1997) α-Synucelin in Lewy bodies. Nature 388: 839–840PubMedCrossRefGoogle Scholar
  38. Tipton KG, Singer TP (1993) Advances in our understanding of the mechanisms of neurotoxicity of MPTP and related compounds. J Neurochem 61: 1191–1206PubMedCrossRefGoogle Scholar
  39. Uèda K, et al (1993) Proc Natl Acad Sci USA 90: 11282–11286PubMedCrossRefGoogle Scholar
  40. Uitti RJ, Calne DB (1993) Pathogenesis of idiopathic parkinsonism. Eur Neurol 33: 6–23PubMedCrossRefGoogle Scholar
  41. Yamada M, Yamada M, Richelson E (1995) Heterogeneity of melanized neurons expressing neurotensin receptor messenger RNA in the substantia nigra and the nucleus paranigralis of control and Parkinson’s disease brain. Neuroscience 64(2): 405–417PubMedCrossRefGoogle Scholar
  42. Zareparsi S, Kaye J, Camicioli R, Grimslid H, Oken B, Litt M, Nutt J, Bird T, Schellenberg G, Payami H (1997) Modulation of the age at onset of Parkinson’s disease by apolipoprotein E genotypes. Ann Neurol 42: 655–658PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • Olaf Riess
    • 1
  • R. Krüger
    • 2
  1. 1.Molecular Human GeneticsRuhr-UniversityBochumFederal Republic of Germany
  2. 2.Department of NeurologyRuhr-University, St. Josef-HospitalBochumFederal Republic of Germany

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