| First Author | Huang X | Year | 2024 |
| Journal | CNS Neurosci Ther | Volume | 30 |
| Issue | 3 | Pages | e14697 |
| PubMed ID | 38544474 | Mgi Jnum | J:347867 |
| Mgi Id | MGI:7625720 | Doi | 10.1111/cns.14697 |
| Citation | Huang X, et al. (2024) BRCC3 mediates inflammation and pyroptosis in cerebral ischemia/reperfusion injury by activating the NLRP6 inflammasome. CNS Neurosci Ther 30(3):e14697 |
| abstractText | AIMS: Neuroinflammation and pyroptosis are key mediators of cerebral ischemia/reperfusion (I/R) injury-induced pathogenic cascades. BRCC3, the human homolog of BRCC36, is implicated in neurological disorders and plays a crucial role in neuroinflammation and pyroptosis. However, its effects and potential mechanisms in cerebral I/R injury in mice are unclear. METHODS: Cellular localization of BRCC3 and the interaction between BRCC3 and NLRP6 were assessed. Middle cerebral artery occlusion/reperfusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) models were established in mice and HT22 cells, respectively, to simulate cerebral I/R injury in vivo and in vitro. RESULTS: BRCC3 protein expression peaked 24 h after MCAO and OGD/R. BRCC3 knockdown reduced the inflammation and pyroptosis caused by cerebral I/R injury and ameliorated neurological deficits in mice after MCAO. The effects of BRCC3 on inflammation and pyroptosis may be mediated by NLRP6 inflammasome activation. Moreover, both BRCC3 and its N- and C-terminals interacted with NLRP6, and both BRCC3 and its terminals reduced NLRP6 ubiquitination. Additionally, BRCC3 affected the interaction between NLRP6 and ASC, which may be related to inflammasome activation. CONCLUSION: BRCC3 shows promise as a novel target to enhance neurological recovery and attenuate the inflammatory responses and pyroptosis caused by NLRP6 activation in cerebral I/R injury. |
