alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies.
alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies.
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发表时间：
1998
影响因子：
11.1
通讯作者：
M. Spillantini;R. Crowther;R. Jakes;M. Hasegawa;M. Goedert
中科院分区：
文献类型：
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作者：
M. Spillantini;R. Crowther;R. Jakes;M. Hasegawa;M. Goedert
路易小体和路易神经突是帕金森病和路易体痴呆的特征性神经病理学特征。它们由成分未知的异常丝状聚集体组成。我们在此表明，来自帕金森病和路易体痴呆的路易小体和路易神经突能被针对α - 突触核蛋白氨基末端和羧基末端序列的抗体强烈染色，表明存在全长或接近全长的α - 突触核蛋白。α - 突触核蛋白染色的结构数量超过了泛素的免疫反应数量，而泛素目前是路易小体和路易神经突最敏感的标记物。因此，α - 突触核蛋白染色将取代泛素染色，成为检测路易小体和路易神经突的首选方法。我们通过一种用于从阿尔茨海默病大脑中提取双螺旋丝的方法分离出了路易小体丝。通过免疫电子显微镜观察，提取出的丝能被抗α - 突触核蛋白抗体强烈标记。5 - 10纳米丝的形态及其染色特征表明，伸展的α - 突触核蛋白分子与丝轴平行，并且这些丝是极性结构。这些发现表明α - 突触核蛋白构成了路易小体和路易神经突的主要丝状成分。
Lewy bodies and Lewy neurites are the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy bodies. They are made of abnormal filamentous assemblies of unknown composition. We show here that Lewy bodies and Lewy neurites from Parkinson's disease and dementia with Lewy bodies are stained strongly by antibodies directed against amino-terminal and carboxyl-terminal sequences of alpha-synuclein, showing the presence of full-length or close to full-length alpha-synuclein. The number of alpha-synuclein-stained structures exceeded that immunoreactive for ubiquitin, which is currently the most sensitive marker of Lewy bodies and Lewy neurites. Staining for alpha-synuclein thus will replace staining for ubiquitin as the preferred method for detecting Lewy bodies and Lewy neurites. We have isolated Lewy body filaments by a method used for the extraction of paired helical filaments from Alzheimer's disease brain. By immunoelectron microscopy, extracted filaments were labeled strongly by anti-alpha-synuclein antibodies. The morphologies of the 5- to 10-nm filaments and their staining characteristics suggest that extended alpha-synuclein molecules run parallel to the filament axis and that the filaments are polar structures. These findings indicate that alpha-synuclein forms the major filamentous component of Lewy bodies and Lewy neurites.