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司来吉兰治疗帕金森病:临床疗效及作用机制推测

Deprenyl in the treatment of Parkinson's disease: clinical effects and speculations on mechanism of action.

作者信息

Olanow C W

机构信息

Mount Sinai School of Medicine, New York, NY, USA.

出版信息

J Neural Transm Suppl. 1996;48:75-84. doi: 10.1007/978-3-7091-7494-4_7.

Abstract

Selegiline is a relatively selective inhibitor of monoamine oxidase type B that has been used in Parkinson's disease as an adjunct to levodopa and as putative neuroprotective therapy. Clinical trials demonstrate that selegiline slows the rate of disease progression and delays the appearance of disability necessitating levodopa. However, confounding symptomatic effects have made it difficult to ascertain the presence of any direct neuroprotective effect. Laboratory studies demonstrate that selegiline protects dopaminergic neurons through a mechanism that does not involve MAO-B inhibition. Recent studies suggest that neuroprotection in laboratory models may be related to the capacity of selegiline to up-regulate a series of anti-oxidant and anti-apoptotic molecules which promote cell survival. Further delineation of the precise mechanism whereby selegiline induces this effect may permit for the development of enhanced neuroprotective benefits in PD patients.

摘要

司来吉兰是一种相对选择性的单胺氧化酶B型抑制剂,已用于帕金森病,作为左旋多巴的辅助药物以及假定的神经保护疗法。临床试验表明,司来吉兰可减缓疾病进展速度,并推迟需要使用左旋多巴的残疾症状出现。然而,混杂的症状性影响使得难以确定是否存在任何直接的神经保护作用。实验室研究表明,司来吉兰通过一种不涉及单胺氧化酶B抑制的机制保护多巴胺能神经元。最近的研究表明,实验室模型中的神经保护作用可能与司来吉兰上调一系列促进细胞存活的抗氧化和抗凋亡分子的能力有关。进一步阐明司来吉兰诱导这种效应的确切机制,可能有助于为帕金森病患者开发增强的神经保护益处。

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