Abstract
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 naïve human scFv library, can recognize oligomers assembled from α-synuclein, amylin, insulin, Aβ40/42, 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 Aβ oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with Aβ levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD.
Keywords: Alzheimer's disease, amyloid, immunotherapy, memory deficit, oligomer, single-chain variable fragment (scFv) antibody.
Current Alzheimer Research
Title:Pan-Amyloid Oligomer Specific scFv Antibody Attenuates Memory Deficits and Brain Amyloid Burden in Mice with Alzheimer’s Disease
Volume: 11 Issue: 1
Author(s): Min Zhao, Shao-wei Wang, Yu-jiong Wang, Ran Zhang, Ya-nan Li, Ya-jing Su, Wei-wei Zhou, Xiao-lin Yu and Rui-tian Liu
Affiliation:
Keywords: Alzheimer's disease, amyloid, immunotherapy, memory deficit, oligomer, single-chain variable fragment (scFv) antibody.
Abstract: 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 naïve human scFv library, can recognize oligomers assembled from α-synuclein, amylin, insulin, Aβ40/42, 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 Aβ oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with Aβ levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD.
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Cite this article as:
Zhao Min, Wang Shao-wei, Wang Yu-jiong, Zhang Ran, Li Ya-nan, Su Ya-jing, Zhou Wei-wei, Yu Xiao-lin and Liu Rui-tian, Pan-Amyloid Oligomer Specific scFv Antibody Attenuates Memory Deficits and Brain Amyloid Burden in Mice with Alzheimer’s Disease, Current Alzheimer Research 2014; 11 (1) . https://dx.doi.org/10.2174/15672050113106660176
DOI https://dx.doi.org/10.2174/15672050113106660176 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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