α-Synuclein oligomers and clinical implications for Parkinson disease.
α-Synuclein oligomers and clinical implications for Parkinson disease.
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DOI：
10.1002/ana.23746
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发表时间：
2013-02
影响因子：
11.2
通讯作者：
Lang, Anthony E.
中科院分区：
文献类型：
--
作者：
Kalia, Lorraine V.;Kalia, Suneil K.;McLean, Pamela J.;Lozano, Andres M.;Lang, Anthony E.
自世纪初以来，中枢神经系统内的蛋白质聚集已被认为是神经退行性疾病的定义特征。从那时起，出现了越来越多的神经退行性疾病，包括帕金森病，其特征在于包含特定的致病蛋白。这导致了长期以来的教条，这些特征性的蛋白质内含物，这是由大的不溶性纤维状蛋白质聚集体和可见的光学显微镜，是负责这些疾病中的细胞死亡。然而，蛋白质内含物形成和细胞毒性之间的相关性是不一致的，表明另一种形式的致病蛋白质可能有助于神经变性。有新的证据表明，可溶性低聚物，较小的蛋白质聚集体无法检测到的常规显微镜，作为潜在的罪魁祸首在神经退行性疾病的发病机制。蛋白质α-突触核蛋白被公认为有助于帕金森病的发病机制，并且是路易体和路易神经突的主要成分。然而，α-突触核蛋白也形成具有对细胞有毒的某些构象的寡聚物种类。这些α-突触核蛋白寡聚体引起细胞死亡的机制正在积极研究，因为它们可能为帕金森病和相关疾病的诊断和治疗提供新的策略。本文综述了α-突触核蛋白寡聚体在帕金森病细胞死亡中的可能作用，并讨论了其潜在的临床意义。
Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20th century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long-held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent suggesting another form of the pathogenic proteins may be contributing to neurodegeneration. There is emerging evidence implicating soluble oligomers, smaller protein aggregates not detectable by conventional microscopy, as potential culprits in the pathogenesis of neurodegenerative diseases. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites. However, α-synuclein also forms oligomeric species with certain conformations being toxic to cells. The mechanisms by which these α-synuclein oligomers cause cell death are being actively investigated as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders. Here we review the possible role of α-synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications.
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