The viruses used in this article from BrainVTA are in the table below

Annexin-A1 (ANXA1) has recently been proposed to play a role in microglial activation after brain ischemia, but the underlying mechanism remains poorly understood. Here, we demonstrated that ANXA1 is modified by SUMOylation, and SUMOylated ANXA1 could promote the beneficial phenotype polarization of microglia. Mechanistically, SUMOylated ANXA1 suppressed nuclear factor κB activation and the production of proinflammatory mediators. Further study revealed that SUMOylated ANXA1 targeted the IκB kinase (IKK) complex and selectively enhanced IKKα degradation. Simultaneously, we detected that SUMOylated ANXA1 facilitated the interaction between IKKα and NBR1 to promote IKKα degradation through selective autophagy. Further work revealed that the overexpression of SUMOylated ANXA1 in microglia/macrophages resulted in marked improvement in neurological function in a mouse model of cerebral ischemia. Collectively, our study demonstrates a previously unidentified mechanism whereby SUMOylated ANXA1 regulates microglial polarization and strongly indicates that up-regulation of ANXA1 SUMOylation in microglia may provide therapeutic benefits for cerebral ischemia.

Figure 1. A proposed working model of SUMOylated ANXA1–mediated microglial anti-inflammatory phenotype polarization after cerebral ischemia.

In this study, the authors developed a method to manipulate gene overexpression in microglia/macrophages in the specific brain areas of animals and provided solid evidence that overexpression of SUMOylated ANXA1 in microglia/macrophages resulted in robust neuroprotection against cerebral ischemic-reperfusion injury. Together, these results indicate that up-regulation of the SUMOylation level of ANXA1 may provide a previously unidentified and potential therapeutic strategy for treating cerebral ischemia.
 

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