IR@PKUHSC  > 北京大学基础医学院
学科主题基础医学
A beta-40 Y10F Increases beta fibrils Formation but Attenuates the Neurotoxicity of Amyloid-beta Peptide
Dai, Xueling1,2; Chang, Ping2; Liu, Wenjuan2; Xu, Ke3; Sun, Yaxuan2; Zhu, Shigong1; Jiang, Zhaofeng2
关键词Alzheimer&prime s disease amyloid-beta peptide beta fibrils neurotoxicity
刊名INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2012-05-01
DOI10.3390/ijms13055324
13期:5页:5324-5337
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary
资助者NSFC ; Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality, PHR (IHLB) ; Scientific Research Common Program of Beijing Municipal Commission of Education ; NSFC ; Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality, PHR (IHLB) ; Scientific Research Common Program of Beijing Municipal Commission of Education
研究领域[WOS]Chemistry
关键词[WOS]ALZHEIMERS-DISEASE ; A-BETA ; OXIDATIVE STRESS ; PROTEIN ; DITYROSINE ; BRAIN ; CYTOTOXICITY ; OLIGOMERS ; BINDING ; NEURODEGENERATION
英文摘要

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.

语种英语
所属项目编号31071512 ; PHR20090514 ; SQKM201211417013
资助者NSFC ; Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality, PHR (IHLB) ; Scientific Research Common Program of Beijing Municipal Commission of Education ; NSFC ; Funding Project for Academic Human Resources Development in Institutions of Higher Learning under the Jurisdiction of Beijing Municipality, PHR (IHLB) ; Scientific Research Common Program of Beijing Municipal Commission of Education
WOS记录号WOS:000306186200003
Citation statistics
Cited Times:6[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66628
Collection北京大学基础医学院
作者单位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
Recommended Citation
GB/T 7714
Dai, Xueling,Chang, Ping,Liu, Wenjuan,et al. A beta-40 Y10F Increases beta fibrils Formation but Attenuates the Neurotoxicity of Amyloid-beta Peptide[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2012,13(5):5324-5337.
APA Dai, Xueling.,Chang, Ping.,Liu, Wenjuan.,Xu, Ke.,Sun, Yaxuan.,...&Jiang, Zhaofeng.(2012).A beta-40 Y10F Increases beta fibrils Formation but Attenuates the Neurotoxicity of Amyloid-beta Peptide.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,13(5),5324-5337.
MLA Dai, Xueling,et al."A beta-40 Y10F Increases beta fibrils Formation but Attenuates the Neurotoxicity of Amyloid-beta Peptide".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 13.5(2012):5324-5337.
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