Saeed Waqar Khalid, Jun Dae Won
Waqar Khalid Saeed, Dae Won Jun, Department of Gastroenterology, Hanyang University School of Medicine, Seoul 133-070, South Korea.
World J Gastroenterol. 2014 Sep 21;20(35):12526-32. doi: 10.3748/wjg.v20.i35.12526.
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.
数十年来,细胞死亡已得到广泛评估,人们也充分认识到,旨在抑制细胞死亡的药物干预可防止大量细胞丢失,从而改善器官的生理功能。长期以来,只有凋亡被视为程序性细胞死亡的唯一形式。最近,坏死性凋亡作为一种RIP1/RIP3依赖性程序性细胞死亡,已被确定为一种具有坏死形态的凋亡备用细胞死亡机制。坏死性凋亡的证据以及通过阻断坏死性凋亡所取得的保护作用,在最近已被广泛报道。然而,只有少数研究报道了在肝脏相关疾病中抑制坏死性凋亡所产生的坏死性凋亡证据及保护作用。尽管坏死性凋亡启动因子的数量在增加;然而,有趣的是,目前仍不清楚在不同的肝脏疾病中究竟是什么实际触发了坏死性凋亡,或者在每种特定疾病状态下是否总是存在不同的坏死性凋亡启动因子以及随之而来的特定下游信号分子。了解坏死性凋亡的确切机制以及对抗肝脏疾病中的其他细胞死亡途径,可能会为实现广泛的治疗意义提供有益的见解。通过靶向坏死性凋亡和/或其他平行死亡途径,可以防止大量细胞丢失,从而防止器官生理功能下降。