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 | |
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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