Advertisement

The Pathophysiological Basis of Parkinson’s Disease

  • M. Gerlach
  • P. Riederer
Chapter
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

Parkinson’s syndrome, or parkinsonism, involving the clinical symptoms first described in 1817 by James Parkinson 1, occurs in a variety of disorders of the central nervous system (CNS), and is basically characterized by dysfunction of the dopaminergic nigro-striatal system. It may, or in rare cases it may not, be associated with distinct anatomical damage to melanin-containing neurons of the substantia nigra (SN), changes in the neuronal cytoskeleton including the presence of Lewy bodies, and pathological changes in other neuronal systems, often as part of a more widespread process 2. The term Parkinson’s disease (PD) is properly restricted to paralysis agitans, the idiopathic form of parkinsonism, associated with the formation of Lewy bodies and the loss of neurons in the pars compacta of the SN (SNC), which has been known since the time of Tretiakoff 3 as the system principally at risk in this disorder. It can be accompanied by nonspecific or age-related brain pathology, and a variety of other coincidental lesions elsewhere in the CNS.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Parkinson J. An essay on the shaking palsy. London: Willingham and Rowland, 1817.Google Scholar
  2. 2.
    Jellinger K. Pathology of Parkinson’s syndrome. In: Calne DB, editor. Handbook of experimental pharmacology, Vol 88. Berlin Heidelberg: Springer-Verlag, 1989: 47- 112.Google Scholar
  3. 3.
    Tretiakoff C. Contribution a l’etude de l’anatomie pathologique du locus niger dissertation. Paris: Univ. of Paris, 1919.Google Scholar
  4. 4.
    Ehringer H, Hornykiewicz O. Verteilung von Noradrenalin und Dopamin (3-Hydroxy- tyramin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Wien Klin Wschr 1960; 72: 1236–9.Google Scholar
  5. 5.
    Birkmayer W, Hornykiewicz O. Der L-Dioxyphenylalanin (l-DOPA) Effekt bei der Parkinson-Akinese. Wien Klin Wschr 1961; 73: 787–8.Google Scholar
  6. 6.
    Barbeau A, Murphy A, Sourkes GF. Excretion of dopamine in diseases of basal ganglia. Science 1961; 133: 1706–8.Google Scholar
  7. 7.
    Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington. J Neurol Sci 1973; 20: 415–55.Google Scholar
  8. 8.
    Birkmayer W, Riederer P. Responsibility of extrastriatal areas for the appearance of psychotic symptoms. J Neural Transm 1975; 37: 175–81.Google Scholar
  9. 9.
    Price KS, Farley IJ, Hornykiewicz O. Neurochemistry of Parkinson’s disease: relation between striatal and limbic dopamine. Adv Biochem Psychopharmacol 1978; 19: 293- 300.Google Scholar
  10. 10.
    Farley IJ, Price KS, Hornykiewicz O. Dopamine in the limbic regions of the human brain: normal and abnormal. Adv Biochem Psychopharmacol 1977; 16: 57–64.Google Scholar
  11. 11.
    Scatton B, Javoy-Agid F, Montfort JC, Agid J. Neurochemistry of monoaminergic neurons in Parkinson’s disease. In: Usdin E, Carlsson A, Dahlström A, Engel J, editors. Catecholamines: Neuropharmacology and central nervous system — therapeutic aspects. New York: Liss A, 1984: 43–52.Google Scholar
  12. 12.
    Riederer P. Wuketich S. Time course of nigrostriatal degeneration in Parkinson’s disease: a detailed study of influential factors in human brain amine analysis. J Neural Transm 1976; 38: 277–301.Google Scholar
  13. 13.
    Riederer P, Sofic E, Konradi C. Neurobiochemische Aspekte zur Progression der Parkinson-Krankheit: Post-mortem-Befunde und MPTP-Modell. In: Fischer PA, editor. Spätsyndrome der Parkinson-Krankheit. Basel: Editiones (Roche), 1986: 37–49.Google Scholar
  14. 14.
    Zetterström T, Sharp T, Collin AK, Ungerstedt U. In vivo measurement of extracellular DA and DOPAC in rat striatum after various DA-releasing drugs: implications for the origin of extracellular DOPAC. Eur J Pharmacol 1988; 148: 327–34.Google Scholar
  15. 15.
    Lloyd K, Hornykiewicz O. Parkinson’s disease: activity of L-dopa decarboxylase in discrete brain regions. Science 1970; 170: 1212–3.Google Scholar
  16. 16.
    Riederer P, Rausch WD, Birkmayer W, Jellinger K, Seemann D. CNS modulation of adrenal tyrosine hydroxylase in Parkinson’s disease and metabolic encephalopathies. J Neural Transm Supplement 1978; 14: 121–32.Google Scholar
  17. 17.
    Rausch WD, Hirata Y, Nagatsu T, Riederer P, Jellinger K. Human brain tyrosine hydroxylase: in vitro effects of iron and phosphorylating agents in the CNS of controls, Parkinson’s disease and schizophrenia. J Neurochem 1988; 50: 202–8.Google Scholar
  18. 18.
    Mogi M, Harada M, Kiuchi K, Kojima K, Kondo T, Narabayashi H, Rausch D, Riederer P, Jellinger K, Nagatsu T. Homospecific activity (activity per enzyme protein) of tyrosine hydroxylase increases in Parkinsonian brain. J Neural Transm 1988; 72: 77–81.Google Scholar
  19. 19.
    Lloyd KG, Davidson L, Homykiewicz O. The neurochemistry of Parkinson’s disease: effect of L-dopa therapy. J Pharmacol Exp Ther 1975; 195: 453–64.Google Scholar
  20. 20.
    Riederer P, Sofic E, Rausch WD, Hebenstreit G, Bruinvels J. Pathobiochemistry of the extrapyramidal system: a “short note” review. In: Przuntek H, Riederer P, editors. Early diagnosis and preventive therapy in Parkinson’s disease. Wien New York: Springer-Verlag, 1989: 139–49.Google Scholar
  21. 21.
    Reichmann H, Riederer P. Biochemische Analyse der Atmungskettenkomplexe verschiedener Hirnregionen von Patienten mit Morbus Parkinson, Symposium des BMFT “Morbus Parkinson und andere Basalganglienerkrankungen”, Bad Kissingen, 1989: 44 2.Google Scholar
  22. 22.
    Nagatsu T, Levitt M, Udenfriend S. Tyrosine hydroxylase: the initial step in norepinephrine biosynthesis. J Biol Chem 1964; 239: 2910–7.Google Scholar
  23. 23.
    Nagatsu T, Yamaguchi T, Kato T, Sugimoto T, Matsuura S, Akino M, Nagatsu I et al. Biopterin in human brain and urine from controls and parkinsonian patients: application of a new radioimmunoassay. Clin Chim Acta 1981; 109: 305–11.Google Scholar
  24. 24.
    Kebabian JW, Calne DB. Multiple receptors for dopamine. Nature 1979; 277: 93–6.Google Scholar
  25. 25.
    Seeman P. Brain dopamine receptors. Pharmacol Rev 1980; 32: 229–313.Google Scholar
  26. 26.
    Zhou QY, Grandy D, Thambi L, Kushner J, Van Tol H, Cone R et al. Cloning and expression of human and rat D1 dopamine receptors. Nature 1990; 347: 76–80.Google Scholar
  27. 27.
    Bunzow J, Van Tol H, Grandy D, Albert P, Salon J, Christie M et al. Cloning and expression of a rat D2 dopamine receptor cDNA. Nature 1988; 336: 783–7.Google Scholar
  28. 28.
    Sokoloff P, Giros P, Martres MP, Bouthenet ML, Schwartz JC. Molecular cloning and characterization of a novel dopamine (D3) receptor as a target for neuroleptics. Nature 1990; 347: 146–51.Google Scholar
  29. 29.
    Wachtel H. Antiparkinsonian dopamine agonists: a review of the pharmacokinetics and neuropharmacology in animals and humans. J Neural Transm P-D Sect 1991; 3: 151 – 201.Google Scholar
  30. 30.
    Markstein R, Vigouret JM. Is D-l receptor stimulation important for the anti-parkin-son activity of dopamine agonists? In: Przuntek H, Riederer P, editors. Early diagnosis and preventive therapy in Parkinson’s disease. Wien New York: Springer-Verlag, 1989: 257–69.Google Scholar
  31. 31.
    Ringwald E, Hirt D, Markstein R, Vigouret JM. Dopamin-Rezeptoren-Stimulation in der Behandlung der Parkinson-Krankheit. Nervenarzt 1982; 53: 67–71.Google Scholar
  32. 32.
    Rinne UK. Brain neurotransmitter receptors in Parkinson’s disease. In: Marsden CD, Fahn S, editors. Movement disorders. London: Butterworths, 1982: 59–74.Google Scholar
  33. 33.
    Stoof JC, Kebabian JW. Opposing roles for D-l and D-2 receptors in efflux of cyclic AMP from rat neostriatum. Nature 1981; 294: 366–8.Google Scholar
  34. 34.
    Girault JA, Spampinato U, Glowinski J, Besson MJ. In vivo release of 3Hgamma-aminobutyric acid in the rat neostriatum. II. Opposing effects of D-l and D-2-dopamine receptor stimulation in the dorsal caudate putamen. Neuroscience 1986; 19: 1109–17.Google Scholar
  35. 35.
    Robertson GS, Robertson HA. D-l and D-2 dopamine agonist synergism: separate sites of action? Trends Pharmacol Sci 1987; 8: 295–9.Google Scholar
  36. 36.
    Raisman R, Cash R, Ruberg M, Javoy-Agid F, Agid Y. Binding of 3HSCH 23390 to D1 receptors in the putamen of control and parkinsonian subjects. Eur J Pharmacol 1985; 113:467–8.Google Scholar
  37. 37.
    Pimoule C, Schoemaker H, Reynolds GP, Langer SZ. 3HSCH 23390 labeled D1 dopamine receptors are unchanged in schizophrenia and Parkinson’s disease. Eur J Pharmacol 1985; 114: 235–7.Google Scholar
  38. 38.
    Rinne JO, Rinne JK, Laakso K, Lönnberg P, Rinne UK. Dopamine D-l receptors in the parkinsonian brain. Brain Res 1985; 359: 306–10.Google Scholar
  39. 39.
    Rinne JO, Laihinen A, Lönnberg P, Marjamäki P, Rinne UK. A post-mortem study on striatal dopamine receptors in Parkinson’s disease. Brain Res 1991; 556: 117–22.Google Scholar
  40. 40.
    Reisine TD, Fields JZ, Yamamura HI, Bird ED, Spokes E, Schreiner PS et al. Neurotransmitter receptor alterations in Parkinson’s disease. Life Sci 1977; 21: 335–44.Google Scholar
  41. 41.
    Lee T, Seeman P, Rajput A, Farley IJ, Hornykiewicz O. Receptor basis for a dopaminergic supersensitivity in Parkinson’s disease. Nature 1978; 273: 59–61.Google Scholar
  42. 42.
    Rinne UK, Sonninen V, Laaksonen H. Responses of brain neurochemistry to levodopa treatment in Parkinson’s disease. In: Poirier LJ, Sourkes TL, Bedard PJ, editors. Advances in neurology, Vol 24. New York: Raven Press, 1979: 259–74.Google Scholar
  43. 43.
    Quik M, Spokes EG, Mackay AVP, Bannister R. Alterations in 3Hspiperone binding in human caudate nucleus, substantia nigra and frontal cortex in the Shy Drager syndrome and Parkinson’s disease. J Neurol Sci 1979; 43: 429–37.Google Scholar
  44. 44.
    Winkler MH, Berl S, Whetsell WO, Yahr MD. Spiroperidol binding in the human caudate nucleus. J Neural Transm 1980; 16: 45–51.Google Scholar
  45. 45.
    Rinne UK, Lönnberg P, Koskinen V. Dopamine receptors in the parkinsonian brain. J Neural Transm 1981; 51: 97–109.Google Scholar
  46. 46.
    Riederer P, Jellinger K. Dopaminerge (D2) Rezeptorfunktion bei Parkinson-Krankheit, Morbus-Alzheimer, seniler Demenz und Schizophrenie. In: Fischer PA, editor. Psychopathologie des Parkinson-Syndroms. Basel: Editiones (Roches), 1982: 71–80.Google Scholar
  47. 47.
    Bokobza B, Ruberg M, Scatton B, Javoy-Agid F, Agid Y. 3HSpiperone binding, dopamine and HVA concentrations in Parkinson’s disease and supranuclear palsy. Eur J Pharmacol 1984; 99: 167–75.Google Scholar
  48. 48.
    Guttman M, Seeman P. L-dopa reverses the elevated density of D2 dopamine receptors in Parkinson’s diseased striatum. J Neural Transm 1985; 64: 93–103.Google Scholar
  49. 49.
    Guttman M, Seeman P, Reynolds GP, Riederer P, Jellinger K, Tourtellotte WW. Dopamine D2 receptor density remains constant in Parkinson’s disease: no explanation for late-onset diminished response to L-dopa. Ann Neurol 1986; 19: 487–92.Google Scholar
  50. 50.
    Seeman P, Bzowej NH, Guan HC, Bergeron C, Reynolds GP, Bird ED et al. Human brain D, and D2 dopamine receptors in schizophrenia, Alzheimer’s disease, Parkinson’s, and Huntington’s diseases. Neuropsychopharmacol 1987; 1: 5–15.Google Scholar
  51. 51.
    Rinne UK, Laihinen A, Rinne JO, Någren K, Bergman J, Ruotsalainen U. Positron emission tomography (PET) demonstrates dopamine D-2 receptor supersensitivity in the striatum of patients with early Parkinson’s disease. Movement Disorders 1990: 5: 55–9.Google Scholar
  52. 52.
    Rinne JO, Laihinen A, Nágren K, Bergman J, Ruotsalainen U, Solin O et al. PET demonstrates different behavior of striatal D1 and D2 receptors in early Parkinson’s disease. J Neurosci Res 1990; 27: 494–9.Google Scholar
  53. 53.
    Riederer P, Rausch WD, Birkmayer W, Jellinger K, Danielczyk W. Dopamine-sensitive adenylate cyclase activity in the caudate nucleus and adrenal medulla in Parkinson’s disease and in liver cirrhosis. J Neural Trans Supplement 1978; 14: 153–61.Google Scholar
  54. 54.
    Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci 1989; 12: 366–75.Google Scholar
  55. 55.
    Alexander GE, Crutcher MD. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 1990; 13: 266–71.Google Scholar
  56. 56.
    Mitchell IJ, Clarke CE, Boyce S, Robertson RG, Peggs D, Sambrook MA et al. Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-de-oxyglucose in monkeys exposed to l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. Neurosci 1989; 32: 213–26.Google Scholar
  57. 57.
    Schwartz WJ, Smith CB, Davidsen L, Savaki H, Sokoloff L. Metabolic mapping of functional activity in the hypothalamo-neurohypophysical system of the rat. Science 1979; 205: 723–5.Google Scholar
  58. 58.
    DeLong MR, Alexander GE, Georgopoulos AP, Crutcher MD, Mitchel SJ, Richardson RT. Role of basal ganglia in limb movements. Human Neurobiol 1984: 2: 235–44.Google Scholar
  59. 59.
    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: 165–76.Google Scholar
  60. 60.
    Kapp W. Benzodiazepine bei Morbus Parkinson. In: Bergmann H, Fitzal S, Kapp W, Steinbereithner K, editors. Benzodiazepine: Klinische Bedeutung und Anwendung. Wien München Bern: Wilhelm Maudrich-Verlag, 1987: 129–35.Google Scholar
  61. 61.
    DeLong MR. Primate models of movement disorders of basal ganglia origin. Trends Neurosci 1990; 13: 281–5.Google Scholar
  62. 62.
    Carmichael SW, Wilson RJ, Brimijoin WS, Melton III LJ, Okazaki H, Yaksh TL et al. Decreased catecholamines in the adrenal medulla of patients with Parkinsonism. New Engl J Med 1988; 318: 254.Google Scholar
  63. 63.
    Stoddard SL, Ahlskog JE, Kelly PJ, Tyce GM, van Heerden JA, Zinsmeister AR et al. Decreased adrenal medullary catecholamines in adrenal transplanted parkinsonian patients compared to nephrectomy patients. Exp. Neurol 1989; 104: 218–22.Google Scholar
  64. 64.
    Harnois C, Dipaolo T. Decreased dopamine in the retinas of patients with Parkinson’s disease. Investigative Opthalmol Visual Sci 1990; 31: 2473–5.Google Scholar
  65. 65.
    Fuxe K, Agnati LF, Kalia M, Goldstein M, Andersson, K, Härfstrand. Dopaminergic systems in the brain and pituitary. In: Flückiger E, Müller EE, Thorner MO, editors. The role of brain dopamine: basic and clinical aspects of neuroscience, Vol 1. Berlin New York: Springer-Verlag, 1985: 11–25.Google Scholar
  66. 66.
    Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmüller B. Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci Lett 1980; 20: 379–82.Google Scholar
  67. 67.
    Riederer P, Kornhuber J, Gerlach M, Danielczyk W, Youdim MBH. Glutamatergic-do-paminergic imbalance in Parkinson’s disease and paranoid hallucinatory psychosis. In: Rinne UK, Nagatsu T, Horowski R, editors. International Workshop Berlin Parkinson’s Disease. Bussum: Medicom Europe, 1991: 10–23.Google Scholar
  68. 68.
    Riederer P, Birkmayer W, Seemann D, Wuketich S. Brain-noradrenaline and 3-methoxy-4-hydroxyphenylglycol in Parkinson’s syndrome. J Neural Transm 1977; 41: 241–51.Google Scholar
  69. 69.
    Scatton B, Javoy-Agid F, Rouquier L, Dubois B, Agid Y. Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson’s disease. Brain Res 1983; 275: 321–8.Google Scholar
  70. 70.
    Bernheimer H, Birkmayer W, Hornykiewicz O. Verteilung des 5-Hydroxytryptamins (Serotonin) im Gehirn des Menschen und sein Verhalten bei Patienten mit Parkinson-Syndrom. Wien Klin Wschr 1961; 39: 1056–9.Google Scholar
  71. 71.
    Rinne UK, Lönnberg P, Koskinen V. Dopamine receptors in the parkinsonian brain. J Neural Transm 1981; 51: 97–106.Google Scholar
  72. 72.
    Lloyd KG, Möhler H, Heitz P, Bartholini G. Distribution of choline acetyltransferase and glutamate decarboxylase within the substantia nigra and in other brain regions from control and parkinsonian patients. J Neurochem 1975; 25: 789–95.Google Scholar
  73. 73.
    Rinne UK, Riekkinen P, Sonninen V, Laaksonen H. Brain acetylcholinesterase in Parkinson’s disease. Acta Neurol Scand 1973; 49: 215–26.Google Scholar
  74. 74.
    McGeer PL, McGeer EG. Enzyme associated with the metabolism of catecholamines, acetylcholine and G AB A in human controls and patients with Parkinson’s disease and Huntington’s chorea. J Neurochem 1976; 26: 65–76.Google Scholar
  75. 75.
    Tarsy D. Dopamine-acetylcholine interaction in the basal ganglia. In: Fields WS, editor. Neurotransmitter function: basic and clinical aspects. New York: Stratton International, 1977: 213–46.Google Scholar
  76. 76.
    Lehmann J, Langer SZ. The striatal cholinergic interneuron: synaptic target of dopaminergic terminals? Neuroscience 1983; 10: 1105–20.Google Scholar
  77. 77.
    Ruberg M, Ploska A, Javoy-Agid F, Agid Y. Muscarinic binding and choline acetyl-transferase activity in parkinsonian subjects with reference to dementia. Brain Res 1982; 232: 129–39.Google Scholar
  78. 78.
    Ruberg M, Rieger F, Villageois A, Bonnet AM, Agid Y. Acetylcholinesterase and butyrylcholinesterase in frontal cortex and cerebrospinal fluid of demented and non-demented patients with Parkinson’s disease. Brain Res 1986; 362: 83–91.Google Scholar
  79. 79.
    Jellinger K. Morphology of Alzheimer’s disease and related disorders. In: Maurer K, Riederer P, Beckmann H, editors. Alzheimer’s disease. Epidemiology, neuropathology, neurochemistry, and clinics. Vienna New York: Springer-Verlag, 1990: 61–77.Google Scholar
  80. 80.
    Moll G, Gsell W, Wichart I, Jellinger K, Riederer P. Cholinergic and monoaminergic neuromediator systems in DAT. Neuropathological and neurochemical findings. In: Maurer K, Riederer P, Beckmann H, editors. Alzheimer’s disease. Epidemiology, neuropathology, neurochemistry, and clinics. Vienna New York: Springer-Verlag, 1990: 235–43.Google Scholar
  81. 81.
    Gaspar P, Javoy-Agid F, Ploska A, Agid Y. Regional distribution of neurotransmitter synthesizing enzymes in the basal ganglia of human brain. J Neurochem 1980; 34: 278–83.Google Scholar
  82. 82.
    Lloyd KG, Hornykiewicz. L-glutamic acid decarboxylase in Parkinson’s disease: effect of L-dopa therapy. Nature 1973; 243: 521–3.Google Scholar
  83. 83.
    Kish SJ, Chang LJ, Mirchandani L, Rajput A, Gilbert J, Rozdilsky B et al. GABA is elevated in striatal but not extrastriatal brain regions in Parkinson’s disease: correlation with striatal dopamine loss. Ann Neurol 1986; 20: 26–31.Google Scholar
  84. 84.
    Perry TL, Javoy-Agid F, Agid Y, Fibiger HC. Striatal GABAergic neuronal acitivity is not reduced in Parkinson’s disease. J Neurochem 1983; 40: 1120–3.Google Scholar
  85. 85.
    Rinne UK, Koskinen V, Laaksonen H, Lönnberg P, Sonninen V. GABA receptor binding in the parkinsonian brain. Life Sci 1978; 22: 2225–8.Google Scholar
  86. 86.
    Perry TL, Hansen S, Gandham SS. Postmortem changes of amino compounds in human and rat brain. J Neurochem 1981; 36: 406–12.Google Scholar
  87. 87.
    Hertz L. Functional interactions between neurons and astrocytes. 1. Turnover and metabolism of putative amino acid transmitters. Prog Neurobio 1979; 13: 277–323.Google Scholar
  88. 88.
    Javoy-Agid F, Ruberg M, Hirsch E, Cash R, Raisman R, Taquet H et al. Recent progress in the neurochemistry of Parkinson’s disease. In: Fahn S, Marsden CD, Jenner P, Teychenne P, editors. Recent developments in Parkinson’s disease. New York: Raven Press, 1986: 67–83.Google Scholar
  89. 89.
    Studier JM, Javoy-Agid F, Cesselin F, Legrand JC, Agid Y. CCK-immunoreactivity distribution in human brain: selective decrease in the substantia nigra from parkinsonian patients. Brain Res 1982; 243: 176–9.Google Scholar
  90. 90.
    Skirboll LR, Grace AA, Hommer DW, Rehfield JG, Goldstein M, Hokfelt T et al. Peptide-monoamine coexistence: studies of the actions of cholecystokinin-like peptide on the electrical activity of mid-brain dopamine neurons. Neuroscience 1981; 6: 2111- 24.Google Scholar
  91. 91.
    Taquet H, Javoy-Agid F, Hamon M, Legrand JC, Agid Y, Cesselin F. Parkinson’s disease affects differently Met5 and Leu5-enkephalin in the human brain. Brain Res 1983; 280: 379–82.Google Scholar
  92. 92.
    Mauborgne A, Javoy-Agid F, Legrand JC, Agid Y, Cesselin F. Decrease of substance P-like immunoreactivity in the substantia nigra and pallidum of parkinsonian brains. Brain Res 1983; 268: 167–70.Google Scholar
  93. 93.
    Rinne UK, Rinne JO, Rinne JK, Laaksonen K, Lönnberg P. Brain neurotransmitters and neuropeptides in Parkinson’s disease. Acta Physiol Pharmacol Latinoam 1984; 34: 287–99.Google Scholar
  94. 94.
    Epelbaum J, Ruberg M, Moyse E, Javoy-Agid F, Dubois B, Agid Y. Somatostatin and dementia in Parkinson’s disease. Brain Res 1983; 278: 376–9.Google Scholar
  95. 95.
    Davies P, Katzman R, Terry RD. Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementia. Nature 1980; 288: 279–80.Google Scholar
  96. 96.
    Strittmater M, Cramer H, Reuner C, Strubel D, Kuntzmann F. Somatostatin-like immunoreactivity and neurotransmitter metabolites in the cerebrospinal fluid of patients with senile dementia of Alzheimer type and Parkinson’s disease. In: Maurer K, Riederer P, Beckmann H, editors. Alzheimer’s disease. Epidemiology, neuropathology, neurochemistry, and clinics. Vienna New York: Springer-Verlag, 1990: 313–21.Google Scholar
  97. 97.
    Hansson E, Rönnbäck L. Astrocytes in neurotransmission. Cell Molec Biol 1990; 36: 487–96.Google Scholar
  98. 98.
    Götz ME, Freyberger A, Riederer P. Oxidative stress: a role in the pathogenesis of Parkinson’s disease. J Neural Transm Supplement 1990; 29: 241–9.Google Scholar
  99. 99.
    Halliwell B, Gutteridge JMC. Oxygen radicals and the nervous system. Trends in Neurosciences 1985; 8: 22–6.Google Scholar
  100. 100.
    Sofic E, Riederer P, Heinsen H, Beckmann H, Reynolds GP, Hebenstreit G. Increased Iron (III) and total iron content in post mortem substantia nigra of Parkinsonian brain. J Neural Transm 1988; 74: 199–205.Google Scholar
  101. 101.
    Riederer P, Sofic E, Rausch WD, Schmidt B, Reynolds GP, Jellinger K et al. Transition metals, ferritin, glutathione and ascorbic acid in parkinsonian brains. J Neurochem 1989; 52: 515–21.Google Scholar
  102. 102.
    Sofic E, Paulus W, Jellinger K, Riederer P, Youdim MBH. Selective increase of iron in substantia nigra zona compacta of parkinsonian brains. J Neurochem 1991; 56: 978–82.Google Scholar
  103. 103.
    Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid F, Lees A et al. Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 1989; 52: 381–9.Google Scholar
  104. 104.
    Konradi C, Svoma E, Jellinger K, Riederer P, Denney RM, Thibault J. Topographic immunocytochemical mapping of monoamine oxidase-A, monoamine oxidase-B and tyrosine hydroxylase in human post mortem brain stem. Neuroscience 1988; 26: 791–802.Google Scholar
  105. 105.
    Westlund KN, Denney RM, Rose RM, Abell CW. Localization of distinct monoamine oxidase A and monoamine oxidase B cell populations in human brain stem. Neuroscience 1988; 25: 439–56.Google Scholar
  106. 106.
    Konradi C, Kornhuber J, Froelich L, Fritze J, Heinsen H, Beckmann H et al. Demonstration of monoamine oxidase-A and B in the human- brainstem by a histo-chemical technique. Neuroscience 1989; 33: 383–400.Google Scholar
  107. 107.
    Jellinger K, Paulus W, Grundke-Iqbal I, Riederer P, Youdim MBH. Brain iron and ferritin in Parkinson’s and Alzheimer’s diseases. J Neural Transm P-D Sect 1990; 2: 327–40.Google Scholar
  108. 108.
    Fischer PA, Schneider E, Jacobi P. Ergebnisse der medikamentösen Parkinson-Therapie. Modifizierende und limitierende Faktoren. In: Fischer PA, editor. Parkinson plus. Berlin New York: Springer-Verlag, 1984: 4–18.Google Scholar
  109. 109.
    Rinne UK. Problems associated with long-term levodopa treatment of Parkinson’s disease. Acta Neurol Scand Supplement 1983; 95: 9–17.Google Scholar
  110. 110.
    Parkes JD. Variability in Parkinson’s disease; clinical aspects, causes and treatment. Acta Neurol Scand Supplement 1983; 95: 27–37.Google Scholar
  111. 111.
    Birkmayer W, Riederer P, editors. Die Parkinson-Krankheit: Biochemie, Klinik, Therapie. 2nd ed. Vienna New York: Springer-Verlag, 1985: 127–36.Google Scholar
  112. 112.
    Birkmayer W, Knoll J, Riederer P, Youdim MBH, Hars V, Marton J. Increased life expectancy resulting from addition of L-deprenyl to MadoparR treatment in Parkinson’s disease: a longterm study. J Neural Transm 1985; 64: 113–27.Google Scholar
  113. 113.
    Tetrud J, Langston W. The effect of deprenyl (selegiline) on the natural history of Parkinson’s disease. Science 1989; 245: 519–22.Google Scholar
  114. 114.
    Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 1989; 321: 1364–71.Google Scholar
  115. 115.
    Gerlach M, Riederer P, Przuntek H, Youdim MBH. MPTP mechanisms of neurotoxicity and their implications for Parkinson’s disease. Eur J Pharmacol Mol Pharmacol Sect 1991; 208: 273–86.Google Scholar

Copyright information

© Springer Basel AG 1993

Authors and Affiliations

  • M. Gerlach
  • P. Riederer

There are no affiliations available

Personalised recommendations