Dec 17, 2018

Novel antibody against oligomeric amyloid-β: Insight into factors for effectively reducing the aggregation and cytotoxicity of amyloid-β aggregates

International Immunopharmacology
Xiaoning ZhangYingjiu Zhang

Abstract

Amyloid-beta 42 (Aβ42) aggregates represent a prominent histopathological feature in Alzheimer's disease (AD); thus, immunotherapy against oligomeric Aβ42 aggregates is considered to be a potentially safe and specific therapeutic strategy. In this study, we identified an anti-oligomeric Aβ42 aggregate single-chain variable fragment (scFv) antibody, HT6, that is capable of efficiently binding to medium-sized Aβ42 aggregates (mainly 18-45 kDa) in vitro with an equilibrium dissociation constant (KD) of 3.0 × 10-6 M, whether they were derived from Aβ42 monomer, larger Aβ42 oligomers, or even fibrils. This ability allowed scFv HT6 to induce the gradual disassembly of large Aβ42 aggregates into small Aβ42 oligomers while simultaneously effectively inhibiting the further development of Aβ42 aggregates. Moreover, the scFv HT6-targeted conformational region on Aβ42 aggregates was found to be more local and relatively close to the N-terminus of Aβ42; thus, scFv HT6 significantly delayed or even prevented the aggregation of Aβ42 protofibrils, while significantly reducing the cytotoxicity of Aβ42 oligomers. Overall, this study demonstrate that even though the decrease in the cytotoxicity of Aβ42 aggregates might be closely related to the r...Continue Reading

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Mentioned in this Paper

Study
Mucocutaneous Lymph Node Syndrome
Alzheimer's Disease
Cytotoxicity
Amyloid Proteins
Protein Aggregation, Pathological
Amyloid
Binding (Molecular Function)
COG1 gene
PGE1 oligomer

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