Deficiency Inhibits Microglial Activation and Alleviates Ischemia-Induced Brain Injury.

Neuroinflammation plays a critical role in ischemia-induced brain injury. Mib2, an E3 ubiquitin ligase, has been reported to regulate Notch signaling and participate in the peripheral immune system. However, the roles of Mib2 in the nervous system are not well characterized. In this study, we show that Mib2 is involved in lipopolysaccharide (LPS)- and oxygen-glucose deprivation (OGD)-induced microglial activation. Mechanistically, Mib2 interacts with the IKK complex and regulates the activation of NF-κB signaling, thus modulating Notch1 transcription in the microglia. Furthermore, we generated a microglia-specific knockout mice and found that microglia-specific deletion of significantly alleviates ischemia-induced neuroinflammation and brain injury. Taken together, our results reveal a critical role of Mib2 in microglial activation and ischemia-induced brain injury, thus providing a potential target for the treatment of stroke.