Apolipoprotein E increases the fibrillogenic potential of synthetic peptides derived from Alzheimer's, gelsolin and AA amyloids.
Apolipoprotein E increases the fibrillogenic potential of synthetic peptides derived from Alzheimer's, gelsolin and AA amyloids.
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载脂蛋白 E 增加源自阿尔茨海默病、凝溶胶蛋白和 AA 淀粉样蛋白的合成肽的纤维化潜力。
DOI：
10.1016/0014-5793(95)00863-5
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发表时间：
1995
期刊：
影响因子：
3.5
通讯作者：
Baumann,M
中科院分区：
文献类型：
--
作者：
Soto,C;Castaño,EM;Prelli,F;Kumar,RA;Baumann,M
载脂蛋白E（apoE）与几种不同类型的系统性和脑淀粉样蛋白沉积有关，并且ApoE 4等位基因的存在构成阿尔茨海默病的危险因素。研究表明，apoE在体外结合并促进阿尔茨海默氏淀粉样蛋白β肽的纤维形成，表明apoE在淀粉样蛋白形成的调节中起重要作用。由于apoE与几种生物化学上不同的淀粉样蛋白沉积物共定位，已经提出apoE在淀粉样变性中起调节和/或参与的一般作用。在本研究中，我们首次表明，载脂蛋白E，从人血浆中分离，增加纤维形成的合成肽，包括凝溶胶蛋白淀粉样蛋白的淀粉样蛋白相关的家族性淀粉样变性芬兰型，和淀粉样蛋白A中发现的继发性淀粉样变性和家族性地中海热的淀粉样蛋白序列。我们的研究结果表明，apoE作为一个一般的病理伴侣在各种淀粉样变性，通过促进可溶性肽转化为淀粉样蛋白形成，病理分子。
Apolipoprotein E (apoE) has been found in association with several differents types of systemic and cerebral amyloid deposits and the presence of the ϵ4 allele constitutes a risk factor for Alzheimer's disease. It has been shown that apoE binds and promotes the fibrillogenesis in vitro of Alzheimer's amyloid β‐peptide, suggesting an important role for apoE in the modulation of amyloidogenesis. Due to the co‐localization of apoE with several biochemically distinct amyloid deposits, it has been proposed that apoE plays a general role modulating and/or participating in amyloidosis. In the present study, we show for the first time that apoE, isolated from human plasma, increases fibril formation of synthetic peptides comprising the amyloidogenic sequences of gelsolin amyloid related to familial amyloidosis Finnish type, and amyloid A found in secondary amyloidosis and familial Mediterranean fever. Our results suggest that apoE acts as a general pathological chaperone in various amyloidoses by enhancing the transition from soluble peptides into amyloid‐forming, pathological molecules.