Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration.
Int J Mol Sci
; 25(6)2024 Mar 20.
Article
in En
| MEDLINE
| ID: mdl-38542478
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 ß. 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Amyloid beta-Peptides
/
Neoplasms
Limits:
Animals
Language:
En
Journal:
Int J Mol Sci
Year:
2024
Document type:
Article
Affiliation country:
Taiwan
Publication country:
CH
/
SUIZA
/
SUÍÇA
/
SWITZERLAND