| First Author | Gannon M | Year | 2022 |
| Journal | eNeuro | Volume | 9 |
| Issue | 3 | PubMed ID | 35697511 |
| Mgi Jnum | J:334645 | Mgi Id | MGI:7295018 |
| Doi | 10.1523/ENEURO.0368-21.2022 | Citation | Gannon M, et al. (2022) 14-3-3theta Does Not Protect against Behavioral or Pathological Deficits in Alzheimer's Disease Mouse Models. eNeuro 9(3):ENEURO.0368-21.2022 |
| abstractText | Alzheimer's disease (AD) is characterized by progressive cognitive impairment associated with synaptic dysfunction and dendritic spine loss and the pathologic hallmarks of beta-amyloid (Abeta) plaques and hyperphosphorylated tau tangles. 14-3-3 proteins are a highly conserved family of proteins whose functions include regulation of protein folding, neuronal architecture, and synaptic function. Additionally, 14-3-3s interact with both Abeta and tau, and reduced levels of 14-3-3s have been shown in the brains of AD patients and in AD mouse models. Here, we examine the neuroprotective potential of the 14-3-3theta isoform in AD models. We demonstrate that 14-3-3theta overexpression is protective and 14-3-3theta inhibition is detrimental against oligomeric Abeta-induced neuronal death in primary cortical cultures. Overexpression of 14-3-3theta using an adeno-associated viral (AAV) vector failed to improve performance on behavioral tests, improve Abeta pathology, or affect synaptic density in the J20 AD mouse model. Similarly, crossing a second AD mouse model, the App(NL-G-F) knock-in (APP KI) mouse, with 14-3-3theta transgenic mice failed to rescue behavioral deficits, reduce Abeta pathology, or impact synaptic density in the APP KI mouse model. 14-3-3theta is likely partially insolubilized in the APP models, as demonstrated by proteinase K digestion. These findings do not support increasing 14-3-3theta expression as a therapeutic approach for AD. |
