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Etiology of Parkinson’s Disease: A Research Strategy

Published online by Cambridge University Press:  18 September 2015

André Barbeau
André Barbeau*
Affiliation:
Department of Neurobiology, Clinical Research Institute of Montreal
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In this essay I present a new “global approach hypothesis” to explain the pathophysiology of Parkinson’s disease: “Susceptibility to Parkinsonism is genetically determined and is reflected in all cells. I propose that idiopathic Parkinson’s disease is the combined result of a generalized cell aging process accelerated, in susceptible individuals, by a variety of often repetitive trigger factors. These factors have in common the fact that they cause a transient increase in turnover within catecholamine producing neurons, centrally as well as peripherally. This results in accumulation within these neurons of free radicals. When the level of the toxic substances, in quantity or in time of exposure, exceeds the scavenging capacity of the cell, damage to organelles and to membranes results, leading to the formation of Lewy bodies through an autoimmune reaction to damaged filaments and to cell death, particularly in the pigmented neurons of the brainstem. The progressive cell depletion leads to a compensatory increase in catecholamine turnover in the remaining pigmented cells, and an ever-accelerating degenerative process. The resulting neurotransmitter imbalance in the basal ganglia explains the symptoms of Parkinson’s disease”. In the light of this hypothesis, our research objectives should be (1) to delineate the limits of true Parkinson’s disease from all phenocopies; (2) to identify individuals susceptible to parkinsonism and the most common trigger factors; (3) to reduce the metabolic effects of unavoidable trigger factors and (4) to protect susceptible individuals by increasing the functional availability of free radical trapping agents.

Type
Special Features
Information
Canadian Journal of Neurological Sciences , Volume 11 , Issue 1 , February 1984 , pp. 24 - 28
Copyright
Copyright © Canadian Neurological Sciences Federation 1984

References

Ambani, L.M.; Van Woert, M.H. and Murphy, S. (1975). Brain peroxidase and catalase in Parkinson’s disease. Arch. Neurol. 32: 114–118.Google Scholar
Barbeau, A. (1969). Parkinson’s disease as a Systemic Disorder Third Symposium on Parkinson’s Disease. Gillingham, F.J. & Donaldson, I.M.L. eds, Edinburgh, pp. 66–73.Google Scholar
Barbeau, A. (1973). Aging and the Extrapyramidal System. J. Amer. Geriatr. Soc. 21: 145–149.Google ScholarPubMed
Barbeau, A. (1983). Manganese and Extrapyramidal disorders. Neurotoxicology – in press.Google Scholar
Barbeau, A. and Pourcher, E. (1982). New Data on the genetics of Parkinson’s Disease. Can. J. Neurol. Sci. 9: 53–60.CrossRefGoogle ScholarPubMed
Barbeau, A. and Roy, M. (1984). Familial subsets in Idiopathic Parkinson’s disease. Can. J. Neurol Sci. – in press.CrossRefGoogle ScholarPubMed
Barbeau, A. and Trombitas, S. (1967). The metabolism of tritium labelled dopamine in Parkinsonian patients. Exerpta Med. Int. Cong. Series. 154: 30–35.Google Scholar
Burns, R.S.; Chiueh, C.C.; Markey, S.P.; Ebert, M.H.; Jacobowitz, D.M. and Kopin, I.J. (1983). A primate model of Parkinsonism: Selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-l, 2, 3, 6, tetrahydropyridine. Proc. Natl. Acad. Sci. 80: 4546–4550.Google Scholar
Davis, G.C.; Williams, A.C.; Markey, S.P; Ebert, M.H.; Caine, E.D.; Reichert, C.M. and Kopin, I.J. (1979). Chronic Parkinsonism secondary to intravenous injection of meperidine. Ann. Psychiat. Res. 1:249–254.CrossRefGoogle ScholarPubMed
Donaldson, J.; McGregor, D. and LaBella, F. (1982). Manganese neurotoxicity: a model forfree radical mediated neurodegeneration? Can. J. Physiol. Pharmacol. 60: 1389–1405.CrossRefGoogle Scholar
Dormandy, T.L. (1983). An approach to free radicals. The Lancet 2: 1010–1014.CrossRefGoogle ScholarPubMed
Goldman, J.E.; Yen, S-H.; Chiu, F.C. and Peress, N.S. (1983). Lewy Bodies of Parkinson’s Disease Contain Neurofilament Antigens. Science 221: 1082–1084.CrossRefGoogle ScholarPubMed
Graham, D.G. (1979). On the origin and significance of neuromelanin. Arch. Pathol. Lab. Med. 103: 359–362.Google ScholarPubMed
Graham, D.G.; Tiffany, S.M. and Bell, W.R. (1978). Auto-oxidation versus covalent binding of quinones as the mechanism of Toxicity of dopamine, 6-Hydroxydopamine and related compounds towards C1300 neuro-blastoma cells in vitro Mol. Pharmacol. 14: 644–653.Google Scholar
Hornykiewicz, O. (1973). Parkinson’s disease: from brain homogenate to treatment. Fed. Proc. 32: 182–190.Google ScholarPubMed
Kondo, K.; Kurland, L.T. and Schull, W.J. (1973). Parkinson’s disease. Genetic Analysis and Evidence of Multifactorial Etiology. Mayo Clinic Proc. 48: 465–475.Google ScholarPubMed
Langston, J.W. and Ballard, P.A. (1983). Parkinson’s Disease in a chemist working with l-Methyl-4-Phenyl-l, 2, 5, 6-Tetrahydropyridine. New Engl. J. Med. 309:310.Google Scholar
Langston, J.W.; Ballard, P.;Tetrud, J.W.;and Irwin, I. (1983). Chronic Parkinsonism in Humans due to a Product of Meperidine-Analog Synthesis. Science 219: 979–980.CrossRefGoogle ScholarPubMed
Mann, D.M.A. and Yates, P.O. (1974a). Lipoprotein pigments—their relationship to aging in the human nervous system. 1. The lipofuscin content of nerve cells. Brain 97: 481–488.Google ScholarPubMed
Mann, D.M.A. and Yates, P.O. (1974b). Lipoprotein pigments—their relationship to aging in the human nervous system. II. The melanin content of pigmented nerve cells. Brain 97: 489–498.CrossRefGoogle ScholarPubMed
Mann, D.M.A.; Yates, P.O. and Barton, C.M. (1977). Melanin and RNA in cells of the human substantia nigra. J. Neuropathol. Exp. Neurol. 36: 379–383.CrossRefGoogle Scholar
Mann, D.M.A.; Yates, P.O.; and Stamp, J.E. (1978). Relationship between lipofuscin and aging in the human nervous system. J. Neurol. Sci. 35: 83–93.CrossRefGoogle Scholar
Mann, D.M.A.; and Yates, P.O. (1979). The effects of aging on the pigmented nerve cells of the human locus caeruleus and substantia nigra. Acta Neuropathol. 47: 93–97.CrossRefGoogle ScholarPubMed
Mann, D.M.A. and Yates, P.O. (1982). Pathogenesis of Parkinson’s Disease. Arch. Neurol. 39: 545–549.CrossRefGoogle ScholarPubMed
Mann, D.M.A. and Yates, P.O. (1983). Possible role of neuromelanin in the Pathogenesis of Parkinson’s Disease. Mechan, of Aging and Develop. I: 193–203.Google Scholar
Martin, W.E.; Yound, W.l. and Anderson, V.E. (1973). Parkinson’s disease—a genetic study. Brain 96: 495–506.Google ScholarPubMed
Perry, T.L.;Godin, D.V. and Hansen, S. (1982). Parkinson’s disease: a disorder due to nigral glutathione deficiency? Neuroscience Letters 33: 305–310.Google ScholarPubMed
Ropper, A.H. (1983). Case Records of the Massachusetts General Hospital-Case 23–1983. New Engl. J. Med. 308: 1406–1414.Google Scholar
Roy, M.; Boyer, L.;and Barbeau, A. (1983). A prospective Study of 50 cases of Familial Parkinson’s Disease. Can. J. Neurol. Sci. 10: 37–42.CrossRefGoogle ScholarPubMed