Spillantini M G, Crowther R A, Jakes R, Hasegawa M, Goedert M
Medical Research Council Centre for Brain Repair and Department of Neurology, University of Cambridge, Robinson Way, Cambridge CB2 2PY, United Kingdom.
Proc Natl Acad Sci U S A. 1998 May 26;95(11):6469-73. doi: 10.1073/pnas.95.11.6469.
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.
路易小体和路易神经突是帕金森病和路易体痴呆的典型神经病理学特征。它们由成分未知的异常丝状聚集体构成。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，显示存在全长或接近全长的α-突触核蛋白。α-突触核蛋白染色结构的数量超过了对泛素免疫反应的结构数量，泛素是目前路易小体和路易神经突最敏感的标志物。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细丝。通过免疫电子显微镜观察，提取的细丝被抗α-突触核蛋白抗体强烈标记。5至10纳米细丝的形态及其染色特征表明，延伸的α-突触核蛋白分子与细丝轴平行排列，且细丝是极性结构。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。
