EFRH-phage immunization of Alzheimer's disease animal model improves behavioral performance in Morris water maze trials

被引:53
作者
Lavie, V
Becker, M
Cohen-Kupiec, R
Yacoby, I
Koppel, R
Wedenig, M
Hutter-Paier, B
Solomon, B [1 ]
机构
[1] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel
[2] JSW Res Co, Graz, Austria
关键词
beta-amyloid; site-directed antibodies; phage-EFRH; cognitive functions;
D O I
10.1385/JMN:24:1:105
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have developed an immunization procedure for the production of effective anti-beta-amyloid (anti-Abeta) antibodies, using filamentous phage displaying only 4 amino acids. The EFRH sequence, encompassing amino acids 3-6 of the 42 residues of Abeta peptide, was found previously to be the main regulatory site for amyloid modulation and the epitope of anti-aggregating antibodies. Engineered filamentous phage enable the display of various numbers of EFRH copies on the phage and serve as potent carriers of antigens. In the present study we have found that phage displaying high EFRH copy number are effective in eliciting humoral response against the EFRH sequence, which in turn relieves the amyloid burden in the brains of amyloid precursor protein Tg mice and improves their ability to perform cognitive tasks.
引用
收藏
页码:105 / 113
页数:9
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