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Novel antibody against oligomeric amyloid-beta: Insight into factors for effectively reducing the aggregation and cytotoxicity of amyloid-beta aggregates 期刊论文

编号：

4c7c905f-7ce1-47c4-84e8-d834bad25ba8
作者：

Zhang, Xiaoning#^[1]Huai, Yangyang#^[1]Cai, Jing(蔡婧)^[1,3]Song, Chuli^[1];Zhang, Yingjiu(张应玖)*^[1,2]
语种：

英文
期刊：

INTERNATIONAL IMMUNOPHARMACOLOGY ISSN：1567-5769 2019 年 67 卷 (176 - 185) ; FEB
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关键词：

scFv antibody Amyloid-beta Alzheimer's disease Aggregation Cytotoxicity
摘要：

Arnyloid-beta 42 (A beta 42) aggregates represent a prominent histopathological feature in Alzheimer's disease (AD); thus, immunotherapy against oligomeric A beta 42 aggregates is considered to be a potentially safe and specific therapeutic strategy. In this study, we identified an anti-oligomeric A beta 42 aggregate single-chain variable fragment (scFv) antibody, HT6, that is capable of efficiently binding to medium-sized A beta 42 aggregates (mainly 18-45 kDa) in vitro with an equilibrium dissociation constant (K-D) of 3.0 x 10(-6) M, whether they were derived from A beta 42 monomer, larger A beta 42 oligomers, or even fibrils. This ability allowed scFv HT6 to induce the gradual disassembly of large A beta 42 aggregates into small A beta 42 oligomers while simultaneously effectively inhibiting the further development of A beta 42aggregates. Moreover, the scFv HT6-targeted conformational region on A beta 42 aggregates was found to be more local and relatively close to the N-terminus of A beta 42; thus, scFv HT6 significantly delayed or even prevented the aggregation of A beta 42 protofibrils, while significantly reducing the cytotoxicity of A beta 42 oligomers. Overall, this study demonstrate that even though the decrease in the cytotoxicity of A beta 42 aggregates might be closely related to the reduction in A beta 42 aggregates and vice versa, the reduction in A beta 42 aggregates might not necessarily be accompanied by or followed by the reduction or even elimination of the cytotoxicity of A beta 42 aggregates. This insight enriches the diversity of anti-oligomeric A beta 42 antibodies, further providing a new understanding into the relationship between their binding pattern to A beta 42 aggregates and the efficacy against their formation, offering a therapeutic strategy to delay the progression of AD.
推荐引用方式
GB/T 7714：

Zhang Xiaoning,Huai Yangyang,Cai Jing, et al. Novel antibody against oligomeric amyloid-beta: Insight into factors for effectively reducing the aggregation and cytotoxicity of amyloid-beta aggregates [J].INTERNATIONAL IMMUNOPHARMACOLOGY,2019,67:176-185.
APA：

Zhang Xiaoning,Huai Yangyang,Cai Jing,Song Chuli,&Zhang Yingjiu.(2019).Novel antibody against oligomeric amyloid-beta: Insight into factors for effectively reducing the aggregation and cytotoxicity of amyloid-beta aggregates .INTERNATIONAL IMMUNOPHARMACOLOGY,67:176-185.
MLA：

Zhang Xiaoning, et al. "Novel antibody against oligomeric amyloid-beta: Insight into factors for effectively reducing the aggregation and cytotoxicity of amyloid-beta aggregates" .INTERNATIONAL IMMUNOPHARMACOLOGY 67(2019):176-185.
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