| First Author | Lin YH | Year | 2022 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 23 | PubMed ID | 36498839 |
| Mgi Jnum | J:334303 | Mgi Id | MGI:7409477 |
| Doi | 10.3390/ijms232314510 | Citation | Lin YH, et al. (2022) Zfra Inhibits the TRAPPC6ADelta-Initiated Pathway of Neurodegeneration. Int J Mol Sci 23(23) |
| abstractText | When WWOX is downregulated in middle age, aggregation of a protein cascade, including TRAPPC6ADelta (TPC6ADelta), TIAF1, and SH3GLB2, may start to occur, and the event lasts more than 30 years, which results in amyloid precursor protein (APP) degradation, amyloid beta (Abeta) generation, and neurodegeneration, as shown in Alzheimer's disease (AD). Here, by treating neuroblastoma SK-N-SH cells with neurotoxin MPP+, upregulation and aggregation of TPC6ADelta, along with aggregation of TIAF1, SH3GLB2, Abeta, and tau, occurred. MPP+ is an inducer of Parkinson's disease (PD), suggesting that TPC6ADelta is a common initiator for AD and PD pathogenesis. Zfra, a 31-amino-acid zinc finger-like WWOX-binding protein, is known to restore memory deficits in 9-month-old triple-transgenic (3xTg) mice by blocking the aggregation of TPC6ADelta, SH3GLB2, tau, and amyloid beta, as well as inflammatory NF-kappaB activation. The Zfra4-10 peptide exerted a strong potency in preventing memory loss during the aging of 3-month-old 3xTg mice up to 9 months, as determined by a novel object recognition task (ORT) and Morris water maize analysis. Compared to age-matched wild type mice, 11-month-old Wwox heterozygous mice exhibited memory loss, and this correlates with pT12-WWOX aggregation in the cortex. Together, aggregation of pT12-WWOX may link to TPC6ADelta aggregation for AD progression, with TPC6ADelta aggregation being a common initiator for AD and PD progression. |
