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为什么我们需要针对帕金森氏症和阿尔茨海默氏症的多功能神经保护和神经修复药物?

Why do we need multifunctional neuroprotective and neurorestorative drugs for Parkinson's and Alzheimer's disorders?

作者信息

Youdim Moussa B H

机构信息

Eve Topf and US National Parkinson Foundation Centers of Excellence for Neurodegenerative Diseases, The Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel, and Department of Biology, Yonsei University, Seoul, Korea.

出版信息

Rambam Maimonides Med J. 2010 Oct 31;1(2):e0011. doi: 10.5041/RMMJ.10011. Print 2010 Oct.

Abstract

Parkinson's disease (PD) and Alzheimer's disease (AD) are severe neurodegenerative disorders, with no drugs that are currently approved to prevent the neuronal cell loss characteristic in brains of patients suffering from PD and AD, and all drug treatments are symptomatic and monomodal in their action. Due to the complex pathophysiology, including a cascade of neurotoxic molecular events that result in neuronal death and predisposition to depression and eventual dementia, and etiology of these disorders, an innovative approach towards neuroprotection or neurorestoration (neurorescue) is the development and use of multifunctional pharmaceuticals which can act at different brain regions and neurons. Such drugs target an array of pathological pathways, each of which is believed to contribute to the cascades that ultimately lead to neuronal cell death. In this short review, we discuss examples of novel multifunctional ligands that may have potential as neuroprotective-neurorestorative therapeutics in PD and AD, some of which are under development. The compounds discussed originate from synthetic chemistry as well as from natural sources.

摘要

帕金森病(PD)和阿尔茨海默病(AD)是严重的神经退行性疾病,目前尚无获批用于预防PD和AD患者大脑中特征性神经元细胞丢失的药物,所有药物治疗均为对症治疗且作用单一。由于这些疾病复杂的病理生理学,包括一系列导致神经元死亡、易患抑郁症并最终发展为痴呆症的神经毒性分子事件以及病因,一种创新的神经保护或神经修复(神经挽救)方法是开发和使用能够作用于不同脑区和神经元的多功能药物。这类药物针对一系列病理途径,据信每条途径都参与了最终导致神经元细胞死亡的级联反应。在这篇简短的综述中,我们讨论了一些新型多功能配体的实例,这些配体可能具有作为PD和AD神经保护 - 神经修复治疗药物的潜力,其中一些仍在研发中。所讨论的化合物来源于合成化学以及天然来源。

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