Author/Authors :
Xu, Yang Xu Department of Neurology - First Affiliated Hospital of Wannan Medical College, Wuhu, China , Zhang, Ji Department of Neurology - First Affiliated Hospital of Wannan Medical College, Wuhu, China , Ma, Lingsong Department of Neurology - First Affiliated Hospital of Wannan Medical College, Wuhu, China , Zhao, Shoucai Department of Neurology - First Affiliated Hospital of Wannan Medical College, Wuhu, China , Li, Shizun Department of Neurology - First Affiliated Hospital of Wannan Medical College, Wuhu, China , Huang, Tingting Department of Neurology - First Affiliated Hospital of Wannan Medical College, Wuhu, China , Chu, Zhaohu Department of Neurology - First Affiliated Hospital of Wannan Medical College, Wuhu, China
Abstract :
Necroptosis is the best-described form of regulated necrosis at present, which is widely recognized as a component of caspase-independent cell death mediated by the concerted action of receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3). Mixed-lineage kinase domain-like (MLKL) was phosphorylated by RIPK3 at the threonine 357 and serine 358 residues and then formed tetramers and translocated onto the plasma membrane, which destabilizes plasma membrane integrity leading to cell swelling and membrane rupture. Necroptosis is downstream of the tumor necrosis factor (TNF) receptor family, and also interaction with NOD-like receptor pyrin 3 (NLRP3) induced inflammasome activation. Multiple inhibitors of RIPK1 and MLKL have been developed to block the cascade of signal pathways for procedural necrosis and represent potential leads for drug development. In this review, we highlight recent progress in the study of roles for necroptosis in cerebral ischemic disease and discuss how these modifications delicately control necroptosis.
