Copper- and iron-induced differential fibril formation in α-synuclein:: TEM study
Copper- and iron-induced differential fibril formation in α-synuclein:: TEM study
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DOI：
10.1016/j.neulet.2007.06.052
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发表时间：
2007-09-07
影响因子：
2.5
通讯作者：
Rao, K. S. J.
中科院分区：
文献类型：
--
作者：
Bharathi;Indi, S. S.;Rao, K. S. J.
α-突触核蛋白丝是帕金森病（PD）和相关病症的特征性胞质内包涵体的中心组分。金属离子是帕金森病的重要致病因素，它们与α-突触核蛋白的相互作用显著影响了纤颤的动力学。目前，我们已经研究了Cu（II）和Fe（III）对α-突触核蛋白原纤维形成的影响。Cu（II）和Fe（III）选择性地和差异性地诱导离散的α-突触核蛋白纤维状物质的形成。在存在和不存在金属离子的情况下，在37 ℃搅拌60小时后，使用透射电子显微镜监测α-突触核蛋白（野生型、A30 P、A53 T和E46 K）的聚集状态。铜（II）诱导薄长网络状原纤维与野生型的α-突触核蛋白，而突变体，显示无定形聚集体，没有原纤维的形式。Fe（III）诱导短而厚的原纤维与野生型和突变型的形式，并与α-突触核蛋白原纤维孵育没有金属离子。本研究说明了金属特异性纤维形态，并在理解金属在神经退行性变中的作用具有相关性。(C)2007爱思唯尔爱尔兰有限公司保留所有权利。
alpha-Synuclein filaments are the central component of intracytoplasmic inclusion bodies characteristic of Parkinson's disease (PD) and related disorders. Metals are the significant etiological factors in PD, and their interaction with alpha-synuclein affect dramatically the kinetics of fibrillation. Currently, we have investigated the influence of Cu(II) and Fe(III) on alpha-synuclein fibril formation. Cu(II) and Fe(III) selectively and differentially induced the formation of discrete alpha-synuclein fibrillar species. Transmission electron microscopy was used to monitor the aggregation state of alpha-synuclein (wild-type, A30P, A53T, and E46K) after 60 h with stirring at 37 degrees C in the presence and absence of metal ions. Cu(II) has induced thin long network-like fibrils with the wild-type of alpha-synuclein, while the mutant, showed amorphous aggregates with no fibrillar forms. Fe(III) induced short and thick fibrils with both wild and mutant forms and were similar to alpha-synuclein fibrils incubated without metal ion. The present study illustrates the metal-specific fibril morphology, and has relevance in understanding the role of metals in neurodegeneration. (C) 2007 Elsevier Ireland Ltd. All rights reserved.