| First Author | Sultanakhmetov G | Year | 2024 |
| Journal | Brain Commun | Volume | 6 |
| Issue | 3 | Pages | fcae136 |
| PubMed ID | 38712317 | Mgi Jnum | J:350520 |
| Mgi Id | MGI:7663036 | Doi | 10.1093/braincomms/fcae136 |
| Citation | Sultanakhmetov G, et al. (2024) Mark4 ablation attenuates pathological phenotypes in a mouse model of tauopathy. Brain Commun 6(3):fcae136 |
| abstractText | Accumulation of abnormally phosphorylated tau proteins is linked to various neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia. Microtubule affinity-regulating kinase 4 (MARK4) has been genetically and pathologically associated with Alzheimer's disease and reported to enhance tau phosphorylation and toxicity in Drosophila and mouse traumatic brain-injury models but not in mammalian tauopathy models. To investigate the role of MARK4 in tau-mediated neuropathology, we crossed P301S tauopathy model (PS19) and Mark4 knockout mice. We performed behaviour, biochemical and histology analyses to evaluate changes in PS19 pathological phenotype with and without Mark4. Here, we demonstrated that Mark4 deletion ameliorated the tau pathology in a mouse model of tauopathy. In particular, we found that PS19 with Mark4 knockout showed improved mortality and memory compared with those bearing an intact Mark4 gene. These phenotypes were accompanied by reduced neurodegeneration and astrogliosis in response to the reduction of pathological forms of tau, such as those phosphorylated at Ser356, AT8-positive tau and thioflavin S-positive tau. Our data indicate that MARK4 critically contributes to tau-mediated neuropathology, suggesting that MARK4 inhibition may serve as a therapeutic avenue for tauopathies. |
