| Autor: |
Chen YA; Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan., Liu TY; Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan., Wen KY; Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan., Hsu CY; Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan., Sze CI; Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan., Chang NS; Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.; Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung 40402, Taiwan.; Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, New York, NY 10314, USA. |
| Abstrakt: |
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. |
