Giasson B I, Uryu K, Trojanowski J Q, Lee V M
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
J Biol Chem. 1999 Mar 19;274(12):7619-22. doi: 10.1074/jbc.274.12.7619.
alpha-Synuclein is a soluble presynaptic protein which is pathologically redistributed within intracellular lesions characteristic of several neurodegenerative diseases. Here we demonstrate that wild type and two mutant forms of alpha-synuclein linked to familial Parkinson's disease (Ala30 --> Pro and Ala53 --> Thr) self-aggregate and assemble into 10-19-nm-wide filaments with distinct morphologies under defined in vitro conditions. Immunogold labeling demonstrates that the central region of all these filaments are more robustly labeled than the N-terminal or C-terminal regions, suggesting that the latter regions are buried within the filaments. Since in vitro generated alpha-synuclein filaments resemble the major ultrastructural elements of authentic Lewy bodies that are hallmark lesions of Parkinson's disease, we propose that self-aggregating alpha-synuclein is the major subunit protein of these filamentous lesions.
α-突触核蛋白是一种可溶性突触前蛋白，在几种神经退行性疾病的细胞内病变中会发生病理性重新分布。在此我们证明，与家族性帕金森病相关的野生型α-突触核蛋白以及两种突变形式（丙氨酸30→脯氨酸和丙氨酸53→苏氨酸）在特定的体外条件下会自我聚集并组装成宽度为10 - 19纳米、形态各异的细丝。免疫金标记显示，所有这些细丝的中央区域比N端或C端区域标记更强，这表明后两个区域埋在细丝内部。由于体外生成的α-突触核蛋白细丝类似于帕金森病标志性病变——真性路易小体的主要超微结构成分，我们提出自我聚集的α-突触核蛋白是这些丝状病变的主要亚基蛋白。
