The potent inhibitory role of suppressing TBK1 in RIPK1 associated cerebral ischemia-reperfusion injury

The pathological mechanism of cell death features in cerebral ischemia-reperfusion injury (CIRI) was compli-cated. The occurrence of various cell death pathways during the progression of ischemia/reperfusion injury promoted complex further neuroinflammation. RIPK1, receptor interacting protein kinase 1, was convinced to be involved in both necroptosis and apoptosis, which is a special RIPK1-dependent apoptosis. More evidences indicated the physiological role of RIPK1 in necroptosis, apoptosis and also autophagy. In this study, we elucidated the RIPK1 exhibited characterization in various cell death pathways in time-course dependent feature. The necroptosis occupied dominant neuron death within 24 h after ischemia/reperfusion injury. However, the neuronal death feature seemed turned to apoptosis 24 h after reperfusion. In this study, it was also found that TBK1 (TANK binding kinase 1) played as suppressor in the regulation of kinase activity of RIPK1. This result might provide a potential approach in mediating the kinase activity of RIPK1 in clinic.

Automated summary

This study revealed that the pathological mechanism of cell death in cerebral ischemia-reperfusion injury is complicated. RIPK1 plays an important role in necroptosis, apoptosis, and autophagy. The dominance of necroptosis in neuronal death is observed within 24 hours after ischemia/reperfusion injury, while apoptosis becomes the predominant feature after 24 hours of reperfusion. Additionally, this study found that TBK1 acts as a suppressor in regulating the kinase activity of RIPK1, providing a potential approach for mediating the kinase activity of RIPK1 in clinical settings.