Orsini F, Argyrousi EK, Restelli E, Ford LK, Takamura H, Matsuzaki S, Zentilin L, Pascente R, Kanaan NM, Soni R, Katayama T, Chiesa R, Forloni G, Kosik KS, Kandel ER, Fraser PE, Arancio O, Fioriti L. SUMO2 Protects Against Tau-induced Synaptic and Cognitive Dysfunction. 2022 Nov 13 10.1101/2022.11.11.516192 (version 1) bioRxiv.
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Sangamo Therapeutics
It’s been almost a decade since the exciting initial discovery of tau SUMOylation by SUMO1, which inhibits degradation of tau and promotes its accumulation. However, it is unknown whether other SUMO isoforms have a similar role. Perhaps surprisingly, these data suggest that SUMO2 appears to have an opposing effect, leading to reduced tau aggregation. Interestingly, mutant tau itself may lower SUMO2 expression due to cell stress, which then could further exacerbate tau toxicity. However, more work will need to be done to understand the underlying mechanism and whether SUMO2 represents an important novel target for treating tauopathies.
View all comments by Amy PoolerMax Planck Institute for Biophysical Chemistry
This highly interesting study supports an important role of sumoylation as a post-translational modification that solubilizes aggregation prone proteins. The study focuses on SUMO2, and it will be interesting to see how modification by SUMO2 compares to modification by SUMO1 with respect to tau pathology in vivo.
From a therapeutic point of view, it is important to understand the specificity of the chaperoning effect of sumoylation and how this would compare to other approaches that use general cell regulation mechanisms for regulating protein solubility in neurodegenerative diseases.
View all comments by Markus ZweckstetterMake a Comment
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