Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke

著者: Masanori Naito, Daichao Xu, Palak Amin, Jinwoo Lee, Huibing Wang, Wanjin Li, Michelle A. Kelliher, Manolis Pasparakis, Junying Yuan - Proceedings of the National Academy of Sciences, PNAS 2020 被引用: 161

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.