Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Necroptosis in Organ Transplantation: Mechanisms and Potential Therapeutic Targets

Version 1 : Received: 4 August 2023 / Approved: 7 August 2023 / Online: 7 August 2023 (12:02:35 CEST)

A peer-reviewed article of this Preprint also exists.

Zhao, Y.; Main, K.; Aujla, T.; Keshavjee, S.; Liu, M. Necroptosis in Organ Transplantation: Mechanisms and Potential Therapeutic Targets. Cells 2023, 12, 2296. Zhao, Y.; Main, K.; Aujla, T.; Keshavjee, S.; Liu, M. Necroptosis in Organ Transplantation: Mechanisms and Potential Therapeutic Targets. Cells 2023, 12, 2296.

Abstract

Organ transplantation remains the only treatment option for patients with end-stage organ dysfunction. However, there are numerous limitations that challenge its clinical application, including the shortage of organ donations, the quality of donated organs, injury during organ preservation and reperfusion, primary and chronic graft dysfunction, acute and chronic rejection, infection, and carcinogenesis in post-transplantation patients. Acute and chronic inflammation and cell death are two major underlying mechanisms for graft injury. Necroptosis is a type of programmed cell death involved in many diseases and has been studied in the setting of all major solid organ transplants, including the kidney, heart, liver, and lung. It is determined by the underlying donor organ conditions (e.g., age, alcohol consumption, fatty liver, hemorrhage shock, donation after circulatory death, etc.), preservation conditions and reperfusion, as well as allograft rejection. Specific molecular mechanisms of necroptosis have been uncovered in the organ transplantation setting, and potential targeting drugs have been identified. We hope this review article will promote more clinical research to determine the role of necroptosis and other types of programmed cell death in solid organ transplantation to alleviate the clinical burden of ischemia-reperfusion injury and graft rejection.

Keywords

programmed cell death; donor organ condition; ischemia reperfusion injury; allograft rejection; inflammation

Subject

Medicine and Pharmacology, Clinical Medicine

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