The toxicity of beta-amyloid is attenuated by interaction with its specific human scFv E3 in vitro.
Beta-amyloid (Abeta) has been suggested as a potent neurotoxic agent. The Abeta-targeted immunotherapy aims to clear diffuse amyloid deposits and reverse memory deficits in Alzheimer's disease. We generated a human single chain variable domain antibody fragment (scFv) against Abeta40, termed E3, by screening a phage antibody library. E3 scFv could recognize Abeta in human cerebral cortex. It was able not only to prevent the aggregation of Abeta but also to disrupt the Abeta preexisting fibrils. Moreover, the Abeta toxicity to SK-N-SH cells was attenuated by addition of E3 scFv. Our results indicate that site-directed human scFv might be a potential therapeutic agent for Alzheimer's disease.
Yue
Shen
S
Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, People's Republic of China.
Li
Yue
Y
Wang
Xiaohua
X
Bai
Hui
H
Xia
Jun
J
Jiang
Li
L
Ji
Yong
Y
Fan
Leming
L
He
Zhigang
Z
Chen
Qi
Q
D000368:Aged; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity* / Q000648:ultrastructure; D000906:Antibodies / Q000302:isolation & purification; D001435:Bacteriophages; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000473:pathology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D011485:Protein Binding / Q000187:drug effects; D020836:Protein Structure, Quaternary
D016229:Amyloid beta-Peptides; D000906:Antibodies; D007135:Immunoglobulin Variable Region