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August 1, 1998

Biochemical aspects of Parkinson's disease

August 1998 issue
51 (2_suppl_2) S2-S9

Abstract

The importance of the striatal dopamine (DA) deficiency and the DA substituting property of levodopa for the pathophysiology and therapy of Parkinson's disease (PD) is reiterated. In addition, it is shown that in PD, significantly reduced DA levels are also found in the nucleus accumbens, external and internal segments of the globus pallidus, the substantia nigra reticulata, and the subthalamic nucleus. It is proposed that, in addition to the critical role played by the striatal DA loss, the DA changes in the extrastriatal nuclei of the basal ganglia are importantly involved in the pathophysiologic mechanisms resulting in the parkinsonian movement disorder, and that the therapeutic and/or side effects of DA substitution therapy may, in part, be mediated through these brain regions which, like the striatum, suffer DAergic deafferentation in PD. From observations in brain of patients with secondary parkinsonism, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine parkinsonism in the rhesus monkey, as well as the regional DA transporter distribution in the primate substantia nigra, it is concluded that PD may be caused by any exogenous and/or endogenous toxin using the transporter system for DA and to some degree the other brain monoamines (noradrenaline, serotonin), to enter, and damage, the respective monoamine neurons. Based on converging evidence, the view is advanced that endogenous, genetically based(excessive) formation, or accumulation, of toxic DA transporter substrates, such as isoquinoline or β-carboline derivatives, may in fact represent the primary cause of substantia nigra cell degeneration in patients with PD.

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Published In

Neurology®
Volume 51Number 2_suppl_2August 1998
Pages: S2-S9
PubMed: 9711973

Publication History

Published online: August 1, 1998
Published in print: August 1998

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Affiliations & Disclosures

Oleh Hornykiewicz, MD
From the Institute of Biochemical Pharmacology, University of Vienna, Austria.

Notes

Address correspondence and reprint requests to Dr. Oleh Hornykiewicz, Institute of Biochemical Pharmacology, Borschkegasse 8a, A-1090 Vienna, Austria.

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