Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke
Masanori Naito, Daichao Xu, Palak Amin, Jinwoo Lee, Huibing Wang, Wanjin Li, Michelle A. Kelliher, Manolis Pasparakis, Junying Yuan
Abstract
deficiency reduces cerebral hemorrhage and delays the onset of neural damage mediated by inflammation. Reduced cerebral perfusion resulting from arterial occlusion promotes the degradation of TAK1, a suppressor of RIPK1, and the transition from necroptosis to apoptosis. Conditional knockout of TAK1 in microglial/infiltrated macrophages and neuronal lineages sensitizes to ischemic infarction by promoting apoptosis. Taken together, our results demonstrate the critical role of necroptosis in mediating neurovascular damage and hypoperfusion-induced TAK1 loss, which subsequently promotes apoptosis and cerebral pathology in stroke and neurodegeneration.