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- Title
Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration.
- Authors
Chen, Yu-An; Liu, Tsung-Yun; Wen, Kuan-Yu; Hsu, Che-Yu; Sze, Chun-I; Chang, Nan-Shan
- Abstract
We reported that a 31-amino-acid Zfra protein (zinc finger-like protein that regulates apoptosis) blocks neurodegeneration and cancer growth. Zfra binds WW domain-containing oxidoreductase (WWOX) to both N- and C-termini, which leads to accelerated WWOX degradation. WWOX limits the progression of neurodegeneration such as Alzheimer's disease (AD) by binding tau and tau-hyperphosphorylating enzymes. Similarly, Zfra binds many protein targets and accelerates their degradation independently of ubiquitination. Furthermore, Zfra4-10 peptide strongly prevents the progression of AD-like symptoms in triple-transgenic (3xTg) mice during aging. Zfra4-10 peptide restores memory loss in 9-month-old 3xTg mice by blocking the aggregation of a protein cascade, including TPC6AΔ, TIAF1, and SH3GLB2, by causing aggregation of tau and amyloid β. Zfra4-10 also suppresses inflammatory NF-κB activation. Zfra-activated Hyal-2+ CD3- CD19- Z cells in the spleen, via Hyal-2/WWOX/Smad4 signaling, are potent in cancer suppression. In this perspective review, we provide mechanistic insights regarding how Zfra overrides WWOX to induce cancer suppression and retard AD progression via Z cells.
- Subjects
OXIDOREDUCTASES; NEURODEGENERATION; PEPTIDES; ALZHEIMER'S disease; ZINC proteins; CARRIER proteins; AMYLOID beta-protein
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 6, p3507
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25063507