Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder characterized by rapidly progressive autonomic and motor dysfunction. Pathologically, MSA is mainly characterized by the abnormal accumulation of misfolded α-synuclein in the cytoplasm of oligodendrocytes, which plays a major role in the pathogenesis of the disease. Striatonigral degeneration and olivopontecerebellar atrophy underlie the motor syndrome, while degeneration of autonomic centers defines the autonomic failure in MSA. At present, there is no treatment that can halt or reverse its progression. However, over the last decade several studies in preclinical models and patients have helped to better understand the pathophysiological events underlying MSA. The etiology of this fatal disorder remains unclear and may be multifactorial, caused by a combination of factors which may serve as targets for novel therapeutic approaches. In this review, we summarize the current knowledge about the etiopathogenesis and neuropathology of MSA, its different preclinical models, and the main disease modifying therapies that have been used so far or that are planned for future clinical trials.

中文翻译：

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MSA：从基本机制到实验疗法。

多系统萎缩症（MSA）是一种罕见的致命性神经退行性疾病，其特征是快速进行性自主神经和运动功能障碍。病理上，MSA的主要特征是在少突胶质细胞的细胞质中错误折叠的α-突触核蛋白异常积累，这在该疾病的发病机理中起着重要作用。纹状体黑质变性和少脑桥小脑萎缩是运动综合症的基础，而自主神经中枢的退化则定义了MSA的自主神经功能衰竭。目前，还没有能够阻止或逆转其进展的治疗方法。但是，在过去的十年中，一些临床前模型和患者研究帮助更好地了解了MSA的病理生理事件。这种致命疾病的病因尚不清楚，可能是多因素的，由多种因素共同作用引起的，这些因素可能会成为新型治疗方法的目标。在这篇综述中，我们总结了有关MSA的病因和神经病理学，其不同的临床前模型以及迄今为止已使用或计划用于未来临床试验的主要疾病改良疗法的当前知识。