SUMOtherapeutics for Ischemic Stroke

The small, ubiquitin-like modifier (SUMO) is a post-translational modifier with a profound influence on several key biological processes, including the mammalian stress response. Of particular interest are its neuroprotective effects, first recognized in the 13-lined ground squirrel (Ictidomys tridecemlineatus), in the context of hibernation torpor. Although the full scope of the SUMO pathway is yet to be elucidated, observations of its importance in managing neuronal responses to ischemia, maintaining ion gradients, and the preconditioning of neural stem cells make it a promising therapeutic target for acute cerebral ischemia. Recent advances in high-throughput screening have enabled the identification of small molecules that can upregulate SUMOylation, some of which have been validated in pertinent preclinical models of cerebral ischemia. Accordingly, the present review aims to summarize current knowledge and highlight the translational potential of the SUMOylation pathway in brain ischemia.

Automated summary

The post-translational modifier SUMO plays a significant role in various biological processes, including the stress response in mammals. Its neuroprotective effects have been observed in hibernation torpor of ground squirrels, suggesting its potential as a therapeutic target for acute cerebral ischemia. Recent advances in screening techniques have identified small molecules that can enhance SUMOylation, and these compounds have shown promise in preclinical models of cerebral ischemia. This review summarizes current knowledge and emphasizes the translational potential of the SUMOylation pathway in brain ischemia.