| First Author | Briner A | Year | 2020 |
| Journal | Cell Rep | Volume | 32 |
| Issue | 7 | Pages | 108045 |
| PubMed ID | 32814048 | Mgi Jnum | J:298889 |
| Mgi Id | MGI:6488912 | Doi | 10.1016/j.celrep.2020.108045 |
| Citation | Briner A, et al. (2020) Fyn Kinase Controls Tau Aggregation In Vivo. Cell Rep 32(7):108045 |
| abstractText | Alzheimer's disease (AD) is a proteinopathy exhibiting aggregation of beta-amyloid (Abeta) as amyloid plaques and tau as neurofibrillary tangles (NFTs), whereas primary tauopathies display only a tau pathology. Abeta toxicity is mediated by Fyn kinase in a tau-dependent process; however, whether Fyn controls tau pathology in diseases that lack Abeta pathology remains unexplored. To address this, we generate the Tg/Fyn(-/-) mouse, which couples mutant tau overexpression with Fyn knockout. Surprisingly, Tg/Fyn(-/-) mice exhibit a near-complete ablation of NFTs, alongside reduced tau hyperphosphorylation, altered tau solubility, and diminished synaptic tau accumulation. Furthermore, Tg/Fyn(-/-) brain lysates elicit less tau seeding in tau biosensor cells. Lastly, the fibrillization of tau is boosted by its pseudophosphorylation at the Fyn epitope Y18. Together, this identifies Fyn as a key regulator of tau pathology independently of Abeta-induced toxicity and thereby represents a potentially valuable therapeutic target for not only AD but also tauopathies more generally. |
