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Pan-Amyloid Oligomer Specific scFv Antibody Attenuates Memory Deficits and Brain Amyloid Burden in Mice with Alzheimer's Disease
Alternative TitleCurr. Alzheimer Res.
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
2014
Source PublicationCURRENT ALZHEIMER RESEARCH
ISSN1567-2050
Volume11Issue:1Pages:69-78
AbstractAmyloid 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.; 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.
KeywordAlzheimer's Disease Amyloid Immunotherapy Memory Deficit Oligomer Single-chain Variable Fragment (Scfv) Antibody
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
URL查看原文
Indexed BySCI
Language英语
WOS KeywordSINGLE-CHAIN ANTIBODY ; HEAT-SHOCK PROTEINS ; A-BETA ; MOUSE MODEL ; CONFORMATION ; CYTOTOXICITY ; RECOGNIZE ; PEPTIDE ; IMMUNOTHERAPY ; NEUROTOXICITY
WOS Research AreaNeurosciences & Neurology
WOS SubjectClinical Neurology ; Neurosciences
WOS IDWOS:000329406700009
Citation statistics
Cited Times:15[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Version出版稿
Identifierhttp://ir.ipe.ac.cn/handle/122111/8158
Collection研究所(批量导入)
Affiliation1.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
Recommended Citation
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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