Necroptosis: a Novel Cell Death Modality and its Potential Relevance for Critical Care Medicine.

Necroptosis: a Novel Cell Death Modality and its Potential Relevance for Critical Care Medicine. Am J Respir Crit Care Med. 2016 Jun 10; Authors: Moreno-Gonzalez G, Vandenabeele P, Krysko DV Abstract Cell death is intertwined with life in development, homeostasis, pathology and ageing. Until recently, apoptosis was the best-known form of programmed cell death, whereas necrosis was for longtime considered accidental due to physicochemical injury. However, identification of crucial signaling and execution molecules, which are highly regulated, revealed that necrosis encompasses several cell death modalities that can be therapeutically targeted. The best understood form of regulated necrosis is necroptosis, which is transduced by the kinase activities of receptor interacting protein kinase-1 (RIPK1) and RIPK3, eventually leading to the activation of mixed lineage kinase domain-like (MLKL) and plasma membrane permeabilization. We are only beginning to appreciate the role of necroptosis in different pathological conditions, including critical illnesses. In this review we discuss the molecular mechanisms of necroptosis and analyze the effect of inhibiting necroptosis in experimental models of critical illnesses. In view of the identification of an increasing number of cell death modalities, we also briefly discuss the simultaneous targeting of multiple cell death modalities because, depending on the cell type and cellular conditions, vario...
Source: American Journal of Respiratory and Critical Care Medicine - Category: Respiratory Medicine Authors: Tags: Am J Respir Crit Care Med Source Type: research