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[帕金森病中针对α-突触核蛋白的新兴疾病修饰策略]

[Emerging Disease-modifying Strategies Targeting α-synuclein in Parkinson's Disease].

作者信息

Hasegawa Takafumi, Kobayashi Junpei, Ishiyama Shun

机构信息

Division of Neurology, Department of Neuroscience and Sensory Organs, Tohoku University Graduate School of Medicine.

出版信息

Brain Nerve. 2020 Feb;72(2):143-150. doi: 10.11477/mf.1416201494.

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Although the standard dopamine replacement therapy can alleviate motor symptoms, presently there is no available treatment to stop or reverse disease progression. Thus, there is an urgent need for the development of novel disease-modifying therapies to prevent the accumulation of cytotoxic α-synuclein (αS), a protein involved in PD pathogenesis, in the nervous system. Furthermore, emerging evidence suggests that the toxic αS species can move from one cell to another, thereby affecting the normal physiological state of the neighboring cells in a prion-like manner. The transmissible, extracellular αS is considered to be an ideal target for the disease-modifying treatments including antibody-based therapy. In this review, we will describe the molecular structure and functions of αS, its relevance to PD pathogenesis, and will discuss the current status and future perspectives of disease-modifying strategies targeting αS in PD.

摘要

帕金森病(PD)是仅次于阿尔茨海默病的第二常见神经退行性疾病。尽管标准的多巴胺替代疗法可以缓解运动症状,但目前尚无有效的治疗方法来阻止或逆转疾病进展。因此,迫切需要开发新的疾病修饰疗法,以防止细胞毒性α-突触核蛋白(αS)在神经系统中积累,αS是一种参与帕金森病发病机制的蛋白质。此外,新出现的证据表明,有毒的αS物种可以从一个细胞转移到另一个细胞,从而以朊病毒样方式影响邻近细胞的正常生理状态。可传播的细胞外αS被认为是包括抗体疗法在内的疾病修饰治疗的理想靶点。在这篇综述中,我们将描述αS的分子结构和功能、其与帕金森病发病机制的相关性,并讨论针对帕金森病中αS的疾病修饰策略的现状和未来前景。

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