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针对帕金森病的α-突触核蛋白靶向治疗。

Targeting alpha-synuclein for the treatment of Parkinson's disease.

机构信息

Department of Biology, Boise State University, Boise, Idaho 83725, USA.

出版信息

CNS Neurol Disord Drug Targets. 2012 Mar;11(2):174-9. doi: 10.2174/187152712800269678.

Abstract

Parkinson's disease (PD) is characterized as a neurodegenerative movement disorder presenting with rigidity, resting tremor, disturbances in balance and slowness in movement. An important pathologic feature of PD is the presence of Lewy bodies. The primary structural component of Lewy bodies are fibrils composed primarily of alpha-synuclein, a highly conserved 140 amino acid protein that is predominantly expressed in neurons and which may play a role in synaptic plasticity and neurotransmission. Numerous studies suggest the aggregation and modification of alpha-synuclein as a key step leading to Lewy body formation and neuronal cell loss associated with PD. Because of the central role of alpha-synuclein in PD, it represents a novel drug target for the possible treatment of this disease. In this review, an overview of the role of alpha-synuclein in PD will be discussed with an emphasis on recent studies utilizing an immunization approach against alpha-synuclein as a possible treatment option for this debilitating disease.

摘要

帕金森病(PD)是一种神经退行性运动障碍,其特征为肌肉僵直、静止性震颤、平衡和运动迟缓。PD 的一个重要病理特征是路易体的存在。路易体的主要结构成分是由主要由α-突触核蛋白组成的纤维,α-突触核蛋白是一种高度保守的 140 个氨基酸的蛋白质,主要在神经元中表达,可能在突触可塑性和神经递质传递中发挥作用。大量研究表明,α-突触核蛋白的聚集和修饰是导致路易体形成和与 PD 相关的神经元细胞丢失的关键步骤。由于α-突触核蛋白在 PD 中的核心作用,它代表了一种新的药物靶点,可能用于治疗这种疾病。在本文综述中,将重点讨论α-突触核蛋白在 PD 中的作用,同时强调利用针对α-突触核蛋白的免疫接种方法作为这种致残性疾病的一种可能治疗选择的最新研究。

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