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Part of the book series: Current Clinical Neurology ((CCNEU))

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Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting millions of patients worldwide. Individuals with parkinsonism develop a slowly progressive and disabling disorder with motor, cognitive, and behavioral symptoms. It is well established that neurodegeneration in this disease affects mainly dopaminergic neurons in the basal ganglia, and recent progress in neuroscience research has begun to establish the pathophysiological links that lead from loss of dopaminergic transmission to the symptoms of parkinsonism. The newly gained knowledge in this area has already resulted in the development of a number of new therapeutic options for patients with PD. The process of neurodegeneration itself is also under very active investigation, primarily using genetic and molecular research. Results from these studies promise to help in the future development of neuroprotective treatments. This chapter outlines the scientific basis for established treatments as well as therapeutic options that are currently under development.

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References

  1. Parkinson J. An Essay on the Shaking Palsy, Sherwood, Neely and Jones, 1817.

    Google Scholar 

  2. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181–184.

    Article  PubMed  CAS  Google Scholar 

  3. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging 2003;24:197–211.

    Article  PubMed  Google Scholar 

  4. Beal MF. Mitochondria, oxidative damage, and inflammation in Parkinson’s disease. Ann N Y Acad Sci 2003;991:120–131.

    Article  PubMed  CAS  Google Scholar 

  5. Cummings JL, Masterman DL. Depression in patients with Parkinson’s disease. Int J Geriatr Psychiatry 1999;14:711–718.

    Article  PubMed  CAS  Google Scholar 

  6. Ichinose H, Ohye T, Takayashi E, et al. Hereditary progressive dystonia with marked diurnal fluctuation caused by mutations in the GTP cyclohydrolase I gene. Nature Genetics 1994;8:236–242.

    Article  PubMed  CAS  Google Scholar 

  7. Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 1997;276:2045–2047.

    Article  PubMed  CAS  Google Scholar 

  8. Trojanowski JQ, Lee VM. “Fatal attractions” of proteins. A comprehensive hypothetical mechanism underlying Alzheimer’s disease and other neurodegenerative disorders. Ann N Y Acad Sci 2000;924: 62–67.

    Article  PubMed  CAS  Google Scholar 

  9. McNaught KS, Olanow CW, Halliwell B, Isacson O, Jenner P. Failure of the ubiquitin-proteasome system in Parkinson’s disease. Nature Reviews Neuroscience 2001;2:589–594.

    Article  PubMed  CAS  Google Scholar 

  10. Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci 1989;12:366–375.

    Article  PubMed  CAS  Google Scholar 

  11. Gerfen CR, Wilson CJ. The Basal Ganglia. In: A Björklund, T HökfeldL Swanson (Eds.), Handbook of Chemical Neuroanatomy, Integrated Systems of the CNS, Part III, Vol., Amsterdam: Elsevier, 1996: 369.

    Google Scholar 

  12. Wichmann T, DeLong MR. Functional neuroanatomy of the basal ganglia in Parkinson’s disease. Adv Neurol 2003;91:9–18.

    PubMed  Google Scholar 

  13. Parent A, Cicchetti F. The current model of basal ganglia organization under scrutiny. Movement Disorders 1998;13:199–202.

    Article  PubMed  CAS  Google Scholar 

  14. Schultz W. The phasic reward signal of primate dopamine neurons. Advances in Pharmacology 1998;42: 686–690.

    Article  PubMed  CAS  Google Scholar 

  15. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nature Neuroscience 2000;3:1301–1306.

    Article  PubMed  CAS  Google Scholar 

  16. Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ. A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 1983; 80:4546–4550.

    Article  PubMed  CAS  Google Scholar 

  17. Kirik D, Annett LE, Burger C, Muzyczka N, Mandel RJ, Bjorklund A. Nigrostriatal alpha-synucleinopathy induced by viral vector-mediated overexpression of human alpha-synuclein: a new primate model of Parkinson’s disease. Proceedings of the National Academy of Sciences of the United States of America 2003;100:2884–2889.

    Article  PubMed  CAS  Google Scholar 

  18. Robertson RG, Graham WC, Sambrook MA, Crossman AR. Further investigations into the pathophysiology of MPTP-induced parkinsonism in the primate: an intracerebral microdialysis study of gamma-aminobutyric acid in the lateral segment of the globus pallidus. Brain Research 1991;563:278–280.

    Article  PubMed  CAS  Google Scholar 

  19. Kojima J, Yamaji Y, Matsumura M, et al. Excitotoxic lesions of the pedunculopontine tegmental nucleus produce contralateral hemiparkinsonism in the monkey. Neurosci Lett 1997;226: 111–114.

    Article  PubMed  CAS  Google Scholar 

  20. Bergman H, Wichmann T, DeLong MR. Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 1990;249:1436–1438.

    Article  PubMed  CAS  Google Scholar 

  21. Wichmann T, Kliem MA, DeLong MR. Antiparkinsonian and behavioral effects of inactivation of the substantia nigra pars reticulata in hemiparkinsonian primates. Exp Neurol 2001;167: 410–424.

    Article  PubMed  CAS  Google Scholar 

  22. Lieberman DM, Corthesy ME, Cummins A, Oldfield EH. Reversal of experimental parkinsonism by using selective chemical ablation of the medial globus pallidus. J Neurosurg 1999;90: 928–934.

    PubMed  CAS  Google Scholar 

  23. Obeso JA, Rodriguez-Oroz MC, Rodriguez M, DeLong MR, Olanow CW. Pathophysiology of levodopa-induced dyskinesias in Parkinson’s disease: problems with the current model. Annals of Neurology 2000;47: S22–32; discussion S32–S24.

    PubMed  CAS  Google Scholar 

  24. Filion M, Tremblay L, Bedard PJ. Abnormal influences of passive limb movement on the activity of globus pallidus neurons in parkinsonian monkeys. Brain Res 1988;444:165–176.

    Article  PubMed  CAS  Google Scholar 

  25. Bergman H, Wichmann T, Karmon B, DeLong MR. The primate subthalamic nucleus. II. Neuronal activity in the MPTP model of parkinsonism. J Neurophysiol 1994;72:507–520.

    PubMed  CAS  Google Scholar 

  26. Bergman H, Wichmann T, DeLong MR. Amelioration of Parkinsonian Symptoms by Inactivation of the Subthalamic Nucleus (STN) in MPTP Treated Green Monkeys. Movement Disorders 1990;5(Suppl 1):79.

    Google Scholar 

  27. Plenz D, Kitai S. A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus. Nature 1999;400:677–682.

    Article  PubMed  CAS  Google Scholar 

  28. Bergman H, Raz A, Feingold A, et al. Physiology of MPTP tremor. Movement Disorders 1998; 13,Suppl. 3:29–34.

    PubMed  Google Scholar 

  29. Bevan MD, Magill PJ, Terman D, Bolam JP, Wilson CJ. Move to the rhythm: oscillations in the subthalamic nucleus-external globus pallidus network. Trends Neurosci 2002;25:525–531.

    Article  PubMed  CAS  Google Scholar 

  30. Brown P. Oscillatory nature of human basal ganglia activity: relationship to the pathophysiology of Parkinson’s disease. Movement Disorders 2003;18:357–363.

    Article  PubMed  Google Scholar 

  31. Schapira AH. Neuroprotection and dopamine agonists. Neurology 2002;58:S9–S18.

    PubMed  CAS  Google Scholar 

  32. Anonymous. DATATOP: a multicenter controlled clinical trial in early Parkinson’s disease. Parkinson Study Group. Arch Neurol 1989;46:1052–1060.

    Google Scholar 

  33. Baron MS, Vitek JL, Bakay RAE, et al. Treatment of advanced Parkinson’s disease by GPi pallidotomy: 1 year pilot-study results. AnnNeurol 1996;40:355–366.

    CAS  Google Scholar 

  34. Gill SS, Heywood P. Bilateral subthalamic nucleotomy can be accomplished safely. Movement Disorders 1998;13:201.

    Google Scholar 

  35. de Bie RM, de Haan RJ, Schuurman PR, Esselink RA, Bosch DA, Speelman JD. Morbidity and mortality following pallidotomy in Parkinson’s disease: a systematic review. Neurology 2002; 58:1008–1012.

    PubMed  Google Scholar 

  36. Ikeda K, Kurokawa M, Aoyama S, Kuwana Y. Neuroprotection by adenosine A2A receptor blockade in experimental models of Parkinson’s disease. J Neurochem 2002;80:262–270.

    Article  PubMed  CAS  Google Scholar 

  37. Greenamyre JT, Eller RV, Zhang Z, Ovadia A, Kurlan R, Gash DM. Antiparkinsonian effects of remacemide hydrochloride, a glutamate antagonist, in rodent and primate models of Parkinson’s disease [comment]. Annals of Neurology 1994;35: 655–661.

    Article  PubMed  CAS  Google Scholar 

  38. Freed CR, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. [comment]. N Engl J Med 2001;344:710–719.

    Article  PubMed  CAS  Google Scholar 

  39. Gash DM, Zhang Z, Ovadia A, et al. Functional recovery in parkinsonian monkeys treated with GDNF. Nature 1996;380:252–255.

    Article  PubMed  CAS  Google Scholar 

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© 2005 Humana Press Inc., Totowa, NJ

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Wichmann, T. (2005). Parkinson’s Disease. In: Tarazi, F.I., Schetz, J.A. (eds) Neurological and Psychiatric Disorders. Current Clinical Neurology. Humana Press. https://doi.org/10.1385/1-59259-856-0:087

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  • DOI: https://doi.org/10.1385/1-59259-856-0:087

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-369-5

  • Online ISBN: 978-1-59259-856-4

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