Abstract
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 Mib2 knockout mice and found that microglia-specific deletion of Mib2 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.
Highlights
Neuroinflammation, generally regarded as a detrimental factor for neurological functions, is involved in various central nervous system (CNS) diseases
We found that the mRNA levels of Mind bomb-2 (Mib2) were significantly increased after LPS stimulation (Supplementary Fig. 1A), indicating that Mib2 might be involved in LPS-induced microglial activation
In the oxygen and glucose deprivation (OGD) model, an in vitro model of ischemia-induced damage, we observed that the mRNA levels of Mib2 were significantly upregulated after 3 h of oxygen-glucose deprivation (OGD) followed by 6 h of reoxygenation (Supplementary Fig. 1B)
Summary
Neuroinflammation, generally regarded as a detrimental factor for neurological functions, is involved in various central nervous system (CNS) diseases. It can be triggered by a variety of stimuli including microbes, brain injury, toxic metabolites, autoimmune response, and neurodegeneration [1,2,3]. Mib KO alleviates ischemic brain injury shown that NF-κB- and Notch-signaling contribute towards the activation of microglia after stroke [12,13,14]. Microglia specific deletion of Mib reduces its activation and neuroinflammation as well as brain damage after ischemic stroke, implicating that Mib might be a potential therapeutic target in stroke treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
