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Zfra restores memory deficits in Alzheimer's disease triple transgenic mice by blocking tau aggregation and amyloid beta formation
Author(s) -
Lin YuHao,
Shih YaoHsiang,
Lee MingHui,
Lin SingRu,
Chang JeanYun,
Sze ChunI,
Kuo YuMin,
Chang NanShan
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.814.9
Subject(s) - transgene , genetically modified mouse , amyloid beta , neuroscience , chemistry , hippocampus , ubiquitin , beta (programming language) , peptide , microbiology and biotechnology , biology , biochemistry , computer science , gene , programming language
Zfra is a naturally occurring 31‐amino‐acid protein. Synthetic peptides Zfra1–31 and Zfra4–10 are known to effectively block the growth of many types of cancer cells. Methods 10‐month‐old triple‐transgenic (3×Tg) mice for Alzheimer's disease (AD) received synthetic Zfra peptides via tail vein injections, followed by examining restoration of memory deficits. Results Zfra significantly down‐regulated tau and amyloid beta (Abeta) aggregates in the brains of 3×Tg mice, and effectively restored their memory capabilities. Zfra inhibited melanoma‐induced neuronal death in the hippocampus and plaque formation in the cortex. Mechanistically, Zfra blocked the aggregation of Abeta42 and many serine‐containing peptides in vitro , and bound cytosolic proteins for accelerating their degradation in ubiquitin/proteasome‐independent manner. Discussion Zfra peptides exhibit a strong efficacy in blocking tau aggregation and Abeta formation and restores memory deficits in 3×Tg mice, suggesting its potential for treatment of AD. Support or Funding Information Department of Defense USA; Ministry of Science and Technology, Taiwan; National Cheng Kung University Top Notch Project