Necroptosis in Cerebral Ischemia

Necroptosis is a form of regulated necrotic cell death, which is mediated by receptor-interacting protein 1 kinase (RIPK1) and RIPK3, and the downstream effector mixed lineage kinase domain-like (MLKL). Necroptotic signals induced by death receptors, such as TNF receptor 1, Toll-like receptors or interferon receptors lead to the formation of the necrosome, and result in cell death with morphological features of necrosis. The execution of necroptosis involves oligomerization of MLKL upon phosphorylation by RIPK3, its translocation to the plasma membrane and consequent plasma membrane permeabilization. Necroptosis participates in physiological functions but is also involved in cell death associated with several pathophysiological conditions. Here, we discuss key features of necroptosis, and evidence implicating necroptotic cell death in brain ischemia.