Zfra restores memory deficits in Alzheimer's disease triple-transgenic mice by blocking aggregation of TRAPPC6AΔ, SH3GLB2, tau, and amyloid β, and inflammatory NF-κB activation

Ming Hui Lee, Yao Hsiang Shih, Sing Ru Lin, Jean Yun Chang, Yu Hao Lin, Chun I. Sze, Yu Min Kuo, Nan Shan Chang

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Introduction Zinc finger-like protein that regulates apoptosis (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 Ten-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 downregulated TRAPPC6AΔ, SH3GLB2, tau, and amyloid β (Αβ) 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 amyloid β 42 and many serine-containing peptides in vitro, suppressed tumor necrosis factor–mediated NF-κB activation, 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 amyloid Αβ formation and restore memory deficits in 3×Tg mice, suggesting its potential for treatment of AD.

Original languageEnglish
Pages (from-to)189-204
Number of pages16
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume3
Issue number2
DOIs
Publication statusPublished - 2017 Jun 1

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Psychiatry and Mental health

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