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 complicated. 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.