Published online Sep 21, 2014. doi: 10.3748/wjg.v20.i35.12526
Revised: June 3, 2014
Accepted: July 15, 2014
Published online: September 21, 2014
Cell death has been extensively evaluated for decades and it is well recognized that pharmacological interventions directed to inhibit cell death can prevent significant cell loss and can thus improve an organ’s physiological function. For long, only apoptosis was considered as a sole form of programmed cell death. Recently necroptosis, a RIP1/RIP3-dependent programmed cell death, has been identified as an apoptotic backup cell death mechanism with necrotic morphology. The evidences of necroptosis and protective effects achieved by blocking necroptosis have been extensively reported in recent past. However, only a few studies reported the evidence of necroptosis and protective effects achieved by inhibiting necroptosis in liver related disease conditions. Although the number of necroptosis initiators is increasing; however, interestingly, it is still unclear that what actually triggers necroptosis in different liver diseases or if there is always a different necroptosis initiator in each specific disease condition followed by specific downstream signaling molecules. Understanding the precise mechanism of necroptosis as well as counteracting other cell death pathways in liver diseases could provide a useful insight towards achieving extensive therapeutic significance. By targeting necroptosis and/or other parallel death pathways, a significant cell loss and thus a decrement in an organ’s physiological function can be prevented.
Core tip: Necroptosis has been identified as apoptotic “back up” cell death mechanism. The evidence of necroptosis and protective effects achieved by blocking necroptosis have been extensively reported in recent past such as in renal ischemic/reperfusion injury, myocardial infarction, and acute pancreatitis. However, only a limited number of studies reported necroptosis evidence and significance of key necroptosis molecules, RIP1 and RIP3, in liver related disease conditions. The current review focuses on evidence of necroptosis in liver related disease conditions as well as potential significance of other programmed necrosis pathways.