Kim Hyun Jin, Chatani Eri, Goto Yuji, Paik Seung R
School of Chemical and Biological Engineering, College of Engineering, Seoul National University, Seoul 151-744, Korea.
J Microbiol Biotechnol. 2007 Dec;17(12):2027-32.
alpha-Synuclein is the major component of Lewy bodies and responsible for the amyloid deposits observed in Parkinson's disease. Ordered filamentous aggregate formation of the natively unfolded a-synuclein was investigated in vitro with the periodic ultrasonication. The ultrasonication induced the fibrillation of a-synuclein, as the random structure gradually converted into a beta-sheet structure. The resulting fibrils obtained at the stationary phase appeared heterogeneous in their size distribution, with the average length and height of 0.28 Mm+/-0.21 Mm and 5.6 nm+/-1.9 nm, respectively. After additional extensive ultrasonication in the absence of monomeric a-synuclein, the equilibrium between the fibril formation and its breakdown shifted to the disintegration of the preexisting fibrils. The resulting fragments served as nucleation centers for the subsequent seed-dependent accelerated fibrillation under a quiescent incubation condition. This self-seeding amplification process depended on the seed formation and subsequent alterations in their properties by the ultrasonication to a state that accretes the monomeric soluble protein more effectively than their reassociation of the seeds back to the original fibrils. Since many neurodegenerative disorders have been considered to be propagated via the seed-dependent amyloidosis, this study would provide a novel aspect of the significance of the seed structure and its properties leading to the accelerated amyloid formation.
α-突触核蛋白是路易小体的主要成分，也是帕金森病中观察到的淀粉样沉积物的成因。利用周期性超声处理在体外研究了天然未折叠的α-突触核蛋白有序丝状聚集体的形成。超声处理诱导了α-突触核蛋白的纤维化，随机结构逐渐转变为β-折叠结构。在稳定期获得的所得纤维在尺寸分布上呈现异质性，平均长度和高度分别为0.28μm±0.21μm和5.6nm±1.9nm。在不存在单体α-突触核蛋白的情况下进行额外的广泛超声处理后，纤维形成与其分解之间的平衡转向预先存在的纤维的解体。所得片段作为随后在静态孵育条件下种子依赖性加速纤维化的成核中心。这种自种子扩增过程取决于种子的形成以及随后通过超声处理使其性质改变为一种比种子重新结合回原始纤维更有效地吸附单体可溶性蛋白的状态。由于许多神经退行性疾病被认为是通过种子依赖性淀粉样变性传播的，这项研究将为种子结构及其性质导致加速淀粉样形成的重要性提供一个新的方面。
