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Zfra restores memory deficits in Alzheimer's disease triple-transgenic mice by blocking aggregation of TRAPPC6A?, SH3GLB2, tau, and amyloid ?, and inflammatory NF-?B activation.


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 TRAPPC6A?, SH3GLB2, tau, and amyloid ? (??) 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 ? 42 and many serine-containing peptides in vitro, suppressed tumor necrosis factor-mediated NF-?B 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 ?? formation and restore memory deficits in 3×Tg mice, suggesting its potential for treatment of AD.

SUBMITTER: Lee MH 

PROVIDER: S-EPMC5651433 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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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.

Lee Ming-Hui MH   Shih Yao-Hsiang YH   Lin Sing-Ru SR   Chang Jean-Yun JY   Lin Yu-Hao YH   Sze Chun-I CI   Kuo Yu-Min YM   Chang Nan-Shan NS  

Alzheimer's & dementia (New York, N. Y.) 20170306 2


<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>Zfra significantly downregulated TRAPPC6AΔ,  ...[more]

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