Department of Biology, Institute for Applied Life Sciences, University of Massachusetts Amherst, Amherst, MA, USA.
Acta Neuropathol. 2021 Jul;142(1):73-86. doi: 10.1007/s00401-020-02163-5. Epub 2020 May 21.
Synucleinopathies are a group of neurodegenerative disorders caused by the misfolding and self-templating of the protein α-synuclein, or the formation of α-synuclein prions. Each disorder differs by age of onset, presenting clinical symptoms, α-synuclein inclusion morphology, and neuropathological distribution. Explaining this disease-specific variability, the strain hypothesis postulates that each prion disease is encoded by a distinct conformation of the misfolded protein, and therefore, each synucleinopathy is caused by a unique α-synuclein structure. This review discusses the current data supporting the role of α-synuclein strains in disease heterogeneity. Several in vitro and in vivo models exist for evaluating strain behavior, however, as the focus of this article is to compare strains across synucleinopathy patients, our discussion predominantly focuses on the two models most commonly used for this purpose: the α-syn140*A53T-YFP cell line and the TgM83 mouse model. Here we define each strain based on biochemical stability, ability to propagate in α-syn140-YFP cell lines, and incubation period, inclusion morphology and distribution, and neurological signs in TgM83 mice.
突触核蛋白病是一组由蛋白质α-突触核蛋白错误折叠和自模板化或α-突触核蛋白朊病毒形成引起的神经退行性疾病。每种疾病的发病年龄、临床表现、α-突触核蛋白包涵体形态和神经病理学分布均不同。为了解释这种疾病特异性的变异性，菌株假说假设每种朊病毒疾病都由错误折叠蛋白的独特构象编码，因此，每种突触核蛋白病都是由独特的α-突触核蛋白结构引起的。这篇综述讨论了支持α-突触核蛋白菌株在疾病异质性中的作用的现有数据。有几种体外和体内模型可用于评估菌株行为，但是，由于本文的重点是比较突触核蛋白病患者中的菌株，因此我们的讨论主要集中在为此目的最常用的两种模型：α-syn140*A53T-YFP 细胞系和TgM83 小鼠模型。在这里，我们根据生化稳定性、在α-syn140-YFP 细胞系中繁殖的能力以及潜伏期、包涵体形态和分布以及 TgM83 小鼠的神经学迹象来定义每种菌株。
