α-突触核蛋白：多系统萎缩朊病毒。
α-Synuclein: Multiple System Atrophy Prions.
机构信息
Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California 94158.
Department of Neurology, University of California, San Francisco, San Francisco, California 94158.
出版信息
Cold Spring Harb Perspect Med. 2018 Jul 2;8(7):a024588. doi: 10.1101/cshperspect.a024588.
Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease arising from the misfolding and accumulation of the protein α-synuclein in oligodendrocytes, where it forms glial cytoplasmic inclusions (GCIs). Several years of studying synthetic α-synuclein fibrils has provided critical insight into the ability of α-synuclein to template endogenous protein misfolding, giving rise to fibrillar structures capable of propagating from cell to cell. However, more recent studies with MSA-derived α-synuclein aggregates have shown that they have a similar ability to undergo template-directed propagation, like PrP prions. Almost 20 years after α-synuclein was discovered as the primary component of GCIs, α-synuclein aggregates isolated from MSA patient samples were shown to infect cultured mammalian cells and also to transmit neurological disease to transgenic mice. These findings argue that α-synuclein becomes a prion in MSA patients. In this review, we discuss the in vitro and in vivo data supporting the recent classification of MSA as a prion disease.
多系统萎缩症（MSA）是一种快速进展的神经退行性疾病，由α-突触核蛋白在少突胶质细胞中的错误折叠和积累引起，在那里它形成神经胶质细胞质包涵体（GCIs）。多年来对合成α-突触核蛋白原纤维的研究为α-突触核蛋白模板内源性蛋白错误折叠的能力提供了重要的见解，导致能够从一个细胞传播到另一个细胞的纤维状结构。然而，最近对 MSA 衍生的α-突触核蛋白聚集体的研究表明，它们具有类似的模板指导传播的能力，就像 PrP 朊病毒一样。在发现 GCIs 的主要成分α-突触核蛋白近 20 年后，从 MSA 患者样本中分离出的α-突触核蛋白聚集体被证明可以感染培养的哺乳动物细胞，并将神经疾病传播给转基因小鼠。这些发现表明α-突触核蛋白在 MSA 患者中成为朊病毒。在这篇综述中，我们讨论了支持最近将 MSA 归类为朊病毒病的体外和体内数据。
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