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Parkinson’s disease — a multifactorial neurodegenerative disorder

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Diagnosis and Treatment of Parkinson’s Disease — State of the Art

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURAL SUPPL,volume 56))

Summary

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.

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References

  • 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: 424–428

    Article  CAS  Google Scholar 

  • 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: 1136–1139

    Article  PubMed  CAS  Google Scholar 

  • Burn DJ, Mark MH, Playford ED, et al (1992) Parkinson’s disease in twins studied with 18F-Dopa and positron emission tomography. Neurology 42: 1894–1900

    Article  PubMed  CAS  Google Scholar 

  • 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): 351–360

    Article  PubMed  CAS  Google Scholar 

  • 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: 154–156

    Article  CAS  Google Scholar 

  • 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: 5104–5108

    Article  PubMed  CAS  Google Scholar 

  • 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: 387–396

    Article  PubMed  CAS  Google Scholar 

  • Gasser T, Müller-Myhsok B, Wszolek ZK, et al (1997) Genetic complexity and Parkinson’s disease. Science 277: 388–389

    PubMed  CAS  Google Scholar 

  • Golbe LI, Di Iorio G, Bonavita V, Miller DC, Duvoisin RC (1990) A large kindred with adPD. Ann Neurol 27: 276–282

    Article  PubMed  CAS  Google Scholar 

  • Golbe LI (1993) A large kindred with PD: onset age, segregation ratios, and anticipation. Mov Disord 8: 406

    Google Scholar 

  • 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): 157–162

    Article  PubMed  CAS  Google Scholar 

  • 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: 6172–6176

    Article  PubMed  CAS  Google Scholar 

  • 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: 181–184

    Article  PubMed  CAS  Google Scholar 

  • Hughes AJ, Daniel SE, Blankson S, Lees AJ (1993) A clinicopathologic study of 100 cases of Parkinson’s disease. Arch Neurol 50: 140–148

    Article  PubMed  CAS  Google Scholar 

  • Hyman C, Hofer M, Barde YA (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350: 230–232

    Article  PubMed  CAS  Google Scholar 

  • 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: 245–253

    Article  PubMed  CAS  Google Scholar 

  • Jellinger KA (1993) Pathogenese und Pathophysiologie der Parkinson-Krankheit. Neuropsychiatrie 7(1): 29–37

    Google Scholar 

  • Jenner P, Schapira AHV, Marsden CD (1992) New insights into the cause of Parkinson’s disease. Neurology 42: 2241–2250

    Article  PubMed  CAS  Google Scholar 

  • 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: 145–147

    Article  PubMed  CAS  Google Scholar 

  • 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): 26–31

    Article  PubMed  CAS  Google Scholar 

  • Kitayama S, Wang J-B, Uhl GR (1993) Deopamine transporter mutants selectively increase MPP+ transport. Synapse 15: 58–62

    Article  PubMed  CAS  Google Scholar 

  • 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: 106–108

    Article  PubMed  Google Scholar 

  • Kurth JH, Kurth MC, Poduloso SE, Schwankhaus JD (1993) Association of a monoamine oxidase B allele with Parkinson’s disease. Ann Neurol 33: 368–372

    Article  PubMed  CAS  Google Scholar 

  • Kurth JH, Eggers-Sedlet B, Liebermann A, Kurth MC (1997) Mov Disord 12(5): 835

    Google Scholar 

  • Langston JW, Irwin I, Langston EB, Forno LS (1984) Pargyline prevents MPTP induced parkinsonism in primates. Science 225: 1480–1482

    Article  PubMed  CAS  Google Scholar 

  • 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: 760–763

    Article  CAS  Google Scholar 

  • 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): 331–339

    Article  PubMed  CAS  Google Scholar 

  • 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: 337–339

    Article  PubMed  Google Scholar 

  • 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: 1589–1593

    Article  PubMed  Google Scholar 

  • Polymeropoulos M, Lavedan C, Leroy E, et al (1997) Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science 276: 2045–2047

    Article  PubMed  CAS  Google Scholar 

  • Riederer P, Konradi C, Hebenstreit G, Youdim MB (1989) Neurochemical perspectives to the function of monoamine oxidase. Acta Neurol Scand [Suppl] 126: 41–45

    Article  CAS  Google Scholar 

  • Schellenberg GD (1995) Genetic dissection of Alzheimer disease, a heterogeneous disorder. Proc Natl Acad Sci USA 92: 8552–8559

    Article  PubMed  CAS  Google Scholar 

  • 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: 475–481

    Article  PubMed  CAS  Google Scholar 

  • 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: 387–388

    Article  PubMed  CAS  Google Scholar 

  • Seeman P, Van Tol HMM (1994) Dopamine receptor pharmacology. TIPS 15: 264–270

    PubMed  CAS  Google Scholar 

  • 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: 1275–1284

    Article  PubMed  CAS  Google Scholar 

  • Spillantini MG, Schmidt ML, Lee VM-Y, Jakes R, Goedert M (1997) α-Synucelin in Lewy bodies. Nature 388: 839–840

    Article  PubMed  CAS  Google Scholar 

  • Tipton KG, Singer TP (1993) Advances in our understanding of the mechanisms of neurotoxicity of MPTP and related compounds. J Neurochem 61: 1191–1206

    Article  PubMed  CAS  Google Scholar 

  • Uèda K, et al (1993) Proc Natl Acad Sci USA 90: 11282–11286

    Article  PubMed  Google Scholar 

  • Uitti RJ, Calne DB (1993) Pathogenesis of idiopathic parkinsonism. Eur Neurol 33: 6–23

    Article  PubMed  Google Scholar 

  • 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): 405–417

    Article  PubMed  CAS  Google Scholar 

  • 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: 655–658

    Article  PubMed  CAS  Google Scholar 

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© 1999 Springer-Verlag Wien

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Riess, O., Krüger, R. (1999). Parkinson’s disease — a multifactorial neurodegenerative disorder. In: Przuntek, H., Müller, T. (eds) Diagnosis and Treatment of Parkinson’s Disease — State of the Art. Journal of Neural Transmission. Supplementa, vol 56. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6360-3_6

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  • DOI: https://doi.org/10.1007/978-3-7091-6360-3_6

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83275-2

  • Online ISBN: 978-3-7091-6360-3

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