Trehalose impairs aggregation of PrPSc molecules and protects prion-infected cells against oxidative damage
Trehalose impairs aggregation of PrPSc molecules and protects prion-infected cells against oxidative damage
复制标题
DOI：
10.1016/j.bbrc.2008.06.094
复制
发表时间：
2008-09-12
影响因子：
3.1
通讯作者：
Lehmann, Sylvain
中科院分区：
文献类型：
--
作者：
Beranger, Florence;Crozet, Carole;Lehmann, Sylvain
神经退行性疾病，如阿尔茨海默氏症、亨廷顿氏症和Pron病，其特征是受影响患者大脑中异常的蛋白质沉积。在Prion疾病中，发病机制中的一个关键事件是将正常的Prion蛋白(PrPC)转化为异常的抗蛋白酶PrPSc沉积，这一现象与体外对氧化应激更高的敏感性有关。在阿尔茨海默病和亨廷顿病的细胞模型中，二糖海藻糖已被证明有效地抑制亨廷顿蛋白和Aβ多肽聚集体，并降低它们相关的毒性。我们在这项研究中表明，海藻糖处理的普鲁恩感染细胞减少了从头产生的PrPSc聚集体的大小，并改变了它们的亚细胞定位。尽管海藻糖不会改变PrPSc分子的抗蛋白酶特性，但它显著保护PrPSc感染的细胞免受诱导的氧化损伤，这表明这种化合物具有治疗意义。(C)2008 Elsevier Inc.保留所有权利。
Neurodegenerative disorders such as Alzheimer's, Huntington's, and prion diseases are characterized by abnormal protein deposits in the brain of affected patients. in prion diseases, a key event in the pathogenesis is the conversion of the normal prion protein (PrPC) into abnormal protease resistant PrPSc deposits, a phenomenon associated with a higher sensitivity to oxidative stress in vitro. In cellular models of Alzheimer and Huntington diseases, the disaccharide trehalose has been shown to be effective in inhibiting huntingtin and A beta peptide aggregates and reducing their associated toxicity. We show in this study that trehalose treatment of prion-infected cells decreases the size of de novo produced PrPSc aggregates and modify their subcellular localization. Despite the fact that trehalose does not modify the protease resistance properties of PrPSc molecules, it significantly protects prion-infected cells from induced oxidative damage, suggesting that this compound is of therapeutic interest. (C) 2008 Elsevier Inc. All rights reserved.