文献类型：期刊文献

英文题名：A beta-40 Y10F Increases beta fibrils Formation but Attenuates the Neurotoxicity of Amyloid-beta Peptide

作者：Dai, Xueling[1,2];Chang, Ping[2];Liu, Wenjuan[2];Xu, Ke[3];Sun, Yaxuan[2];Zhu, Shigong[1];Jiang, Zhaofeng[2]

第一作者：戴雪伶;Dai, Xueling

通讯作者：Zhu, SG[1]

机构：[1]Peking Univ, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Beijing 100191, Peoples R China;[2]Beijing Union Univ, Beijing Key Lab Bioact Subst & Funct Foods, Beijing 100191, Peoples R China;[3]Capital Normal Univ, Coll Life Sci, Beijing 100048, Peoples R China

第一机构：Peking Univ, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Beijing 100191, Peoples R China

通讯机构：[1]corresponding author), Peking Univ, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Beijing 100191, Peoples R China.

年份：2012

卷号：13

期号：5

起止页码：5324-5337

外文期刊名：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

收录：;Scopus(收录号：2-s2.0-84861563553);WOS:【SCI-EXPANDED(收录号:WOS:000306186200003)】；

基金：This work was supported by grants from NSFC Project 31071512, grants from the Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality, PHR (IHLB) [PHR20090514] and from Scientific Research Common Program of Beijing Municipal Commission of Education (SQKM201211417013).

语种：英文

外文关键词：Alzheimer's disease; amyloid-beta peptide; beta fibrils; neurotoxicity

摘要：Alzheimer's disease (AD) is characterized by the abnormal aggregation of amyloid-beta peptide (A beta) in extracellular deposits known as senile plaques. The tyrosine residue (Tyr-10) is believed to be important in A beta-induced neurotoxicity due to the formation of tyrosyl radicals. To reduce the likelihood of cross-linking, here we designed an A beta-40 analogue (A beta-40 Y10F) in which the tyrosine residue was substituted by a structurally similar residue, phenylalanine. The aggregation rate was determined by the Thioflavin T (ThT) assay, in which A beta-40 Y10F populated an ensemble of folded conformations much quicker and stronger than the wild type A beta. Biophysical tests subsequently confirmed the results of the ThT assay, suggesting the measured increase of beta-aggregation may arise predominantly from enhancement of hydrophobicity upon substitution and thus the propensity of intrinsic beta-sheet formation. Nevertheless, A beta-40 Y10F exhibited remarkably decreased neurotoxicity compared to A beta-40 which could be partly due to the reduced generation of hydrogen peroxide. These findings may lead to further understanding of the structural perturbation of A beta to its fibrillation.