Whittaker Heather T, Qui Yichen, Bettencourt Conceição, Houlden Henry
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, UK.
F1000Res. 2017 Nov 30;6:2072. doi: 10.12688/f1000research.12193.1. eCollection 2017.
Multiple system atrophy (MSA) is one of the few neurodegenerative disorders where we have a significant understanding of the clinical and pathological manifestations but where the aetiology remains almost completely unknown. Research to overcome this hurdle is gaining momentum through international research collaboration and a series of genetic and molecular discoveries in the last few years, which have advanced our knowledge of this rare synucleinopathy. In MSA, the discovery of α-synuclein pathology and glial cytoplasmic inclusions remain the most significant findings. Families with certain types of α-synuclein mutations develop diseases that mimic MSA, and the spectrum of clinical and pathological features in these families suggests a spectrum of severity, from late-onset Parkinson's disease to MSA. Nonetheless, controversies persist, such as the role of common α-synuclein variants in MSA and whether this disorder shares a common mechanism of spreading pathology with other protein misfolding neurodegenerative diseases. Here, we review these issues, specifically focusing on α-synuclein mutations.
多系统萎缩（MSA）是少数几种我们对其临床和病理表现有深入了解但病因几乎完全未知的神经退行性疾病之一。通过国际研究合作以及过去几年的一系列基因和分子发现，克服这一障碍的研究正在加速推进，这些发现增进了我们对这种罕见的α-突触核蛋白病的认识。在多系统萎缩中，α-突触核蛋白病理学和胶质细胞胞质内含物的发现仍然是最重要的发现。具有某些类型α-突触核蛋白突变的家族会患上类似多系统萎缩的疾病，这些家族的临床和病理特征谱表明了从晚发性帕金森病到多系统萎缩的严重程度谱。尽管如此，争议仍然存在，例如常见α-突触核蛋白变体在多系统萎缩中的作用，以及这种疾病是否与其他蛋白质错误折叠神经退行性疾病共享病理传播的共同机制。在这里，我们回顾这些问题，特别关注α-突触核蛋白突变。
