Pan-Amyloid Oligomer Specific scFv Antibody Attenuates Memory Deficits and Brain Amyloid Burden in Mice with Alzheimer's Disease
Zhao, Min1,2; Wang, Shao-wei1,3; Wang, Yu-jiong3; Zhang, Ran1,3; Li, Ya-nan1; Su, Ya-jing1; Zhou, Wei-wei1; Yu, Xiao-lin1; Liu, Rui-tian1
刊名CURRENT ALZHEIMER RESEARCH
2014
卷号11期号:1页码:69-78
关键词Alzheimer's disease amyloid immunotherapy memory deficit oligomer single-chain variable fragment (scFv) antibody
ISSN号1567-2050
其他题名Curr. Alzheimer Res.
中文摘要Amyloid oligomers have a critical function in the pathologic processes of various amyloidoses, such as Alzheimer's disease (AD), Parkinson disease (PD), Huntington's disease, prion-related diseases, type 2 diabetes, and hereditary renal amyloidosis. Our previous reports demonstrated that a conformation-dependent oligomer-specific single-chain variable fragment (scFv) antibody, W20, isolated from a naive human scFv library, can recognize oligomers assembled from alpha-synuclein, amylin, insulin, A beta 40/42, prion peptide 106-126, and lysozyme, inhibit the aggregation of various amyloid, and attenuate amyloid oligomer-induced cytotoxicity In vitro. Furthermore, W20 recognized the amyloid oligomers in all types of plaques, Lewy bodies, and amylin deposits in the brain tissues of AD and PD patients and in the pancreas of type 2 diabetes patients. In the current study, we showed that W20 blocked the binding of A beta oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with A beta levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD.
英文摘要Amyloid oligomers have a critical function in the pathologic processes of various amyloidoses, such as Alzheimer's disease (AD), Parkinson disease (PD), Huntington's disease, prion-related diseases, type 2 diabetes, and hereditary renal amyloidosis. Our previous reports demonstrated that a conformation-dependent oligomer-specific single-chain variable fragment (scFv) antibody, W20, isolated from a naive human scFv library, can recognize oligomers assembled from alpha-synuclein, amylin, insulin, A beta 40/42, prion peptide 106-126, and lysozyme, inhibit the aggregation of various amyloid, and attenuate amyloid oligomer-induced cytotoxicity In vitro. Furthermore, W20 recognized the amyloid oligomers in all types of plaques, Lewy bodies, and amylin deposits in the brain tissues of AD and PD patients and in the pancreas of type 2 diabetes patients. In the current study, we showed that W20 blocked the binding of A beta oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with A beta levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD.
WOS标题词Science & Technology ; Life Sciences & Biomedicine
类目[WOS]Clinical Neurology ; Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]SINGLE-CHAIN ANTIBODY ; HEAT-SHOCK PROTEINS ; A-BETA ; MOUSE MODEL ; CONFORMATION ; CYTOTOXICITY ; RECOGNIZE ; PEPTIDE ; IMMUNOTHERAPY ; NEUROTOXICITY
收录类别SCI
原文出处://WOS:000329406700009
语种英语
WOS记录号WOS:000329406700009
公开日期2014-05-06
内容类型期刊论文
版本出版稿
源URL[http://ir.ipe.ac.cn/handle/122111/8158]  
专题过程工程研究所_研究所(批量导入)
作者单位1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China
3.Ningxia Univ, Sch Life Sci, Yinchuan 750021, Peoples R China
推荐引用方式
GB/T 7714
Zhao, Min,Wang, Shao-wei,Wang, Yu-jiong,et al. Pan-Amyloid Oligomer Specific scFv Antibody Attenuates Memory Deficits and Brain Amyloid Burden in Mice with Alzheimer's Disease[J]. CURRENT ALZHEIMER RESEARCH,2014,11(1):69-78.
APA Zhao, Min.,Wang, Shao-wei.,Wang, Yu-jiong.,Zhang, Ran.,Li, Ya-nan.,...&Liu, Rui-tian.(2014).Pan-Amyloid Oligomer Specific scFv Antibody Attenuates Memory Deficits and Brain Amyloid Burden in Mice with Alzheimer's Disease.CURRENT ALZHEIMER RESEARCH,11(1),69-78.
MLA Zhao, Min,et al."Pan-Amyloid Oligomer Specific scFv Antibody Attenuates Memory Deficits and Brain Amyloid Burden in Mice with Alzheimer's Disease".CURRENT ALZHEIMER RESEARCH 11.1(2014):69-78.
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