Department of Anatomy, School of Medicine, Konkuk University, 120 Neungdong-Ro, Gwangjin-gu, Seoul, 05029, South Korea.
Research Institute of Medical Science, Konkuk University, Seoul, 05029, South Korea.
Exp Mol Med. 2019 Nov 18;51(11):1-10. doi: 10.1038/s12276-019-0346-8.
Multiple system atrophy (MSA) is a neurodegenerative disease with diverse clinical manifestations, including parkinsonism, cerebellar syndrome, and autonomic failure. Pathologically, MSA is characterized by glial cytoplasmic inclusions in oligodendrocytes, which contain fibrillary forms of α-synuclein. MSA is categorized as one of the α-synucleinopathy, and α-synuclein aggregation is thought to be the culprit of the disease pathogenesis. Studies on MSA pathogenesis are scarce relative to studies on the pathogenesis of other synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies. However, recent developments in cellular and animal models of MSA, especially α-synuclein transgenic models, have driven advancements in research on this disease. Here, we review the currently available models of MSA, which include toxicant-induced animal models, α-synuclein-overexpressing cellular models, and mouse models that express α-synuclein specifically in oligodendrocytes through cell type-specific promoters. We will also discuss the results of studies in recently developed transmission mouse models, into which MSA brain extracts were intracerebrally injected. By reviewing the findings obtained from these model systems, we will discuss what we have learned about the disease and describe the strengths and limitations of the models, thereby ultimately providing direction for the design of better models and future research.
多系统萎缩（MSA）是一种具有多种临床表现的神经退行性疾病，包括帕金森病、小脑综合征和自主神经衰竭。病理学上，MSA 的特征是少突胶质细胞内的神经胶质细胞质包涵体，其中包含α-突触核蛋白的纤维形式。MSA 被归类为α-突触核蛋白病之一，α-突触核蛋白聚集被认为是疾病发病机制的罪魁祸首。与其他突触核蛋白病（如帕金森病和路易体痴呆）的发病机制研究相比，对 MSA 发病机制的研究相对较少。然而，MSA 的细胞和动物模型，特别是α-突触核蛋白转基因模型的最新进展，推动了对该疾病的研究进展。在这里，我们回顾了目前可用的 MSA 模型，包括毒素诱导的动物模型、α-突触核蛋白过表达的细胞模型，以及通过细胞类型特异性启动子在少突胶质细胞中特异性表达α-突触核蛋白的小鼠模型。我们还将讨论最近开发的传播性小鼠模型的研究结果，这些模型中脑内注射了 MSA 脑提取物。通过回顾这些模型系统中获得的发现，我们将讨论我们对该疾病的了解，并描述模型的优势和局限性，从而为更好的模型设计和未来的研究提供方向。
