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 language | English |
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Pages (from-to) | 189-204 |
Number of pages | 16 |
Journal | Alzheimer's and Dementia: Translational Research and Clinical Interventions |
Volume | 3 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2017 Jun 1 |
All Science Journal Classification (ASJC) codes
- Clinical Neurology
- Psychiatry and Mental health