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Lee MH, Shih YH, Lin SR, et al. 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. Alzheimers Dement (N Y). 2017;3(2):189-204doi: 10.1016/j.trci.2017.02.001.
Lee, M. H., Shih, Y. H., Lin, S. R., Chang, J. Y., Lin, Y. H., Sze, C. I., Kuo, Y. M., & Chang, N. S. (2017). 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. Alzheimer's & dementia (New York, N. Y.), 3(2), 189-204. https://doi.org/10.1016/j.trci.2017.02.001
Lee, Ming-Hui, et al. "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." Alzheimer's & dementia (New York, N. Y.) vol. 3,2 (2017): 189-204. doi: https://doi.org/10.1016/j.trci.2017.02.001
Lee MH, Shih YH, Lin SR, Chang JY, Lin YH, Sze CI, Kuo YM, Chang NS. 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. Alzheimers Dement (N Y). 2017 Mar 06;3(2):189-204. doi: 10.1016/j.trci.2017.02.001. eCollection 2017 Jun. PMID: 29067327; PMCID: PMC5651433.
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Alzheimers Dement (N Y). 2017 Mar 06;3(2):189-204. doi: 10.1016/j.trci.2017.02.001. eCollection 2017 Jun.

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.

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

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

Affiliations

  1. Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
  2. Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
  3. Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan, Taiwan, ROC.
  4. Center of Infectious Disease and Signaling Research, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
  5. Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan, ROC.
  6. Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, New York, NY, USA.

PMID: 29067327 PMCID: PMC5651433 DOI: 10.1016/j.trci.2017.02.001

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.

Keywords: Neurodegeneration; Peptide polymerization; Protein degradation; SH3GLB2; TRAPPC6A; WWOX; Zfra

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