Intracellular Trafficking SNARE Protein, Syntaxin-6, is a Modifier of Prion and Tau Pathogenesis in vivo and in Cellular Models
Hill, E.; Patel, M.; Ribes, J. M.; Linehan, J.; Zhang, F.; Farmer, M.; Jakubcova, T.; Hamdan, S.; Tomlinson, A.; Ercolani, T.; Schmidt, C.; Ahmed, P.; Thirlway, G.; Purro, S.; Argentina, F.; Marinho, A. T.; Jones, E. L.; Kaye, N.; Fitzhugh, C.; de Silva, R.; Jackson, G. S.; Brandner, S.; Kloehn, P.; Collinge, J.; Cunningham, T. J.; Mead, S.
Show abstract
Syntaxin-6, a SNARE protein involved in intracellular protein trafficking, is a proposed risk factor for sporadic prion disease, progressive supranuclear palsy and Alzheimers disease. However, no study has validated its functional role in these diseases, explored the disease stage at which it is acting nor its mechanism of action. Here, we show that syntaxin-6 acts at early stages of prion disease in experimental mice by increasing disease transmission risk following inoculation with low prion doses. Conversely, syntaxin-6 does not affect prion propagation kinetics or toxicity during established disease. Syntaxin-6 manipulation in cellular models profoundly alters the subcellular distribution and morphologies of disease-related PrP and modifies prion export. Furthermore, syntaxin-6 knockout in a transgenic tauopathy mouse model exerts protective effects on numerous physiological, behavioural and neuropathological outcome measures. Therefore, our studies firmly establish syntaxin-6 as a modifier of prion and tau pathogenesis, providing key insights into a fundamental mechanism of neurodegeneration.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in an Alzheimer's disease model 96%
- Molecular characterization of selectively vulnerable neurons in Alzheimer's Disease 96%
- TREM2 interacts with TDP-43 and mediates microglial neuroprotection against TDP-43-related neurodegeneration 96%
Similar papers in this journal
Similar papers in this journal
- Neurons burdened by DNA double strand breaks incite microglia activation through antiviral-like signaling in neurodegeneration. 95%
- Copper drives prion protein phase separation and modulates aggregation 95%
- Tau pathology spreads between anatomically-connected regions of the brain and is modulated by a LRRK2 mutation 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.