Multiple System Atrophy: Pathology, Pathogenesis, and Path Forward

IF 2.9 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemistry Biochemistry Pub Date : 2024-10-15 DOI:10.1146/annurev-pathmechdis-051122-104528
Alain Ndayisaba, Glenda M. Halliday, Vikram Khurana
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Abstract

Multiple system atrophy (MSA) is a fatal neurodegenerative disease characterized by autonomic failure and motor impairment. The hallmark pathologic finding in MSA is widespread oligodendroglial cytoplasmic inclusions rich in aggregated α-synuclein (αSyn). MSA is widely held to be an oligodendroglial synucleinopathy, and we outline lines of evidence to support this assertion, including the presence of early myelin loss. We consider emerging data that support the possibility of neuronal or immune dysfunction as primary drivers of MSA. These hypotheses are placed in the context of a major recent discovery that αSyn is conformationally distinct in MSA versus other synucleinopathies such as Parkinson's disease. We outline emerging techniques in epidemiology, genetics, and molecular pathology that will shed more light on this mysterious disease. We anticipate a future in which cutting-edge developments in personalized disease modeling, including with pluripotent stem cells, bridge mechanistic developments at the bench and real benefits at the bedside.
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多系统萎缩:病理学、发病机制和前进之路
多系统萎缩症(MSA)是一种致命的神经退行性疾病,以自主神经功能衰竭和运动障碍为特征。MSA的标志性病理发现是广泛的少突胶质细胞质包涵体富含聚集的α-突触核蛋白(αSyn)。人们普遍认为 MSA 是一种少突胶质突触核蛋白病,我们概述了支持这一观点的证据,包括早期髓鞘脱失的存在。我们考虑了新出现的数据,这些数据支持神经元或免疫功能障碍作为 MSA 主要驱动因素的可能性。最近的一项重大发现表明,αSyn 在 MSA 中的构象与帕金森病等其他突触核蛋白病不同。我们概述了流行病学、遗传学和分子病理学方面的新兴技术,这些技术将为这一神秘疾病带来更多启示。我们预计,未来个性化疾病建模的前沿发展,包括多能干细胞,将为工作台的机理发展和床边的实际获益架起桥梁。
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来源期刊
Biochemistry Biochemistry
Biochemistry Biochemistry 生物-生化与分子生物学
CiteScore
5.50
自引率
3.40%
发文量
336
审稿时长
1-2 weeks
期刊介绍: Biochemistry provides an international forum for publishing exceptional, rigorous, high-impact research across all of biological chemistry. This broad scope includes studies on the chemical, physical, mechanistic, and/or structural basis of biological or cell function, and encompasses the fields of chemical biology, synthetic biology, disease biology, cell biology, nucleic acid biology, neuroscience, structural biology, and biophysics. In addition to traditional Research Articles, Biochemistry also publishes Communications, Viewpoints, and Perspectives, as well as From the Bench articles that report new methods of particular interest to the biological chemistry community.
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