A rationale for monoamine oxidase inhibition as neuroprotective therapy for parkinson's disease
作者:
C. W. Olanow,
期刊:
Movement Disorders
(WILEY Available online 1993)
卷期:
Volume 8,
issue S1
页码: 1-7
ISSN:0885-3185
年代: 1993
DOI:10.1002/mds.870080503
出版商: Wiley Subscription Services, Inc., A Wiley Company
关键词: parkinson's disease;oxidant stress;iron and aluminum accumulation;hydroxyl free radicals;MAO‐B inhibition;selegiline (L‐deprenyl)
数据来源: WILEY
摘要:
AbstractNeurons in the substantia nigra may be vulnerable to oxidant stress because (a) the metabolism of dopamine generates peroxides, which, in the presence of iron, can lead to the formation of the highly reactive hydroxyl free radical; and (b) neuromelanin within nigral neurons can bind metals such as iron and aluminum and thereby promote the site‐specific formation of free radicals. Postmortem studies show increased iron, decreased glutathione, and increased lipid peroxidation in the substantia nigra of patients with Parkinson's disease (PD). Recent studies also report iron and aluminum accumulation within neuromelanin granules of patients with PD. These findings suggest that the substantia nigra in the patient with PD is in a state of oxidant stress and that antioxidant therapy might protect residual dopamine neurons and slow the natural progression of PD. Selective inhibitors of monoamine oxidase type B (MAO‐B) have been chosen for study because of their capacity to interfere with the oxidative metabolism of dopamine and so diminish the likelihood that free radicals will be formed. Initial studies demonstrate that the MAO‐B inhibitorL‐deprenyl (selegiline) delays the development of disability in otherwise untreated patients with early Parkinson's disease. Although the mechanism responsible for these observationsremains unclear, these results are consistent with the possibility that L‐deprenyl provides neuroprotectiv
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