期刊
MOLECULAR IMMUNOLOGY
卷 45, 期 4, 页码 881-886出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2007.08.008
关键词
Alzheimer's disease; single-chain fv (scFv) antibodies; amyloid-beta; neurotoxicity; ADDLs; immunotherapy
资金
- NIA NIH HHS [R0-1 AG20241, AG023534] Funding Source: Medline
- NINDS NIH HHS [R0-1 NS50895] Funding Source: Medline
Active and passive immunotherapy targeted at the amyloid-beta (A beta) peptide has been proposed as therapeutic approach against Alzheimer's disease (AD), and efforts towards the generation and application of antibody-based reagents that are capable of preventing and clearing amyloid aggregates are currently under active investigation. Previously, we selected and characterized a new anti-A beta(1-42) phage-displayed scFv antibody, designated clone b4.4, using a non-immune human scFv antibody library and demonstrated that a peptide based on the sequence of the Ig heavy chain (V-H) complementarity-determining region (HCDR3) of this antibody fragment bound to A beta(1-42) and had neuroprotective potential against A beta(1-42) mediated neurotoxicity in rat hippocampal cultured neurons. In the present study, using novel computational methods and in vitro experiments we demonstrated that b4.4 binds to the central region of A beta(1-42). We also demonstrated that this scFv antibody binds to A beta-derived diffusible ligands (ADDLs) and neutralizes the toxicity of both fibrillar and oligomeric forms of A beta(1-42) tested in vitro in SH-SY5Y cell cultures. (c) 2007 Elsevier Ltd. All rights reserved.
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