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α-突触核蛋白生物合成中的蛋白质-蛋白质相互作用:帕金森病的新潜在靶点。

Protein-Protein Interactions in Alpha-Synuclein Biogenesis: New Potential Targets in Parkinson's Disease.

作者信息

Hernandez Sarah M, Tikhonova Elena B, Karamyshev Andrey L

机构信息

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, United States.

出版信息

Front Aging Neurosci. 2020 Mar 17;12:72. doi: 10.3389/fnagi.2020.00072. eCollection 2020.

Abstract

Parkinson's disease (PD) is a debilitating neurodegenerative disorder defined by a loss of dopamine-producing neurons in the substantia nigra in the brain. It is associated with cytosolic inclusions known as Lewy bodies. The major component of Lewy bodies is aggregated alpha-synuclein. The molecular mechanism of alpha-synuclein aggregation is not known. Our conceptual model is that alpha-synuclein aggregates due to a dysregulation of its interactions with other protein partners that are required for its biogenesis. In this mini review article, we identified alpha-synuclein interactions using both current literature and predictive pathway analysis. Alterations of these interactions may be crucial elements for the molecular mechanism of the protein aggregation and related pathology in the disease. Identification of alpha-synuclein interactions provides valuable tools to understand PD pathology and find new pharmacological targets for disease treatment.

摘要

帕金森病(PD)是一种使人衰弱的神经退行性疾病,其特征是大脑黑质中产生多巴胺的神经元丧失。它与被称为路易小体的胞质内含物有关。路易小体的主要成分是聚集的α-突触核蛋白。α-突触核蛋白聚集的分子机制尚不清楚。我们的概念模型是,α-突触核蛋白由于其与生物合成所需的其他蛋白质伙伴相互作用失调而聚集。在这篇小型综述文章中,我们利用当前文献和预测性通路分析确定了α-突触核蛋白的相互作用。这些相互作用的改变可能是该疾病中蛋白质聚集和相关病理学分子机制的关键因素。确定α-突触核蛋白的相互作用为理解帕金森病病理学和寻找疾病治疗的新药理学靶点提供了有价值的工具。

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