Understanding necroptosis and its therapeutic target for intervertebral disc degeneration

Abstract

Intervertebral disc degeneration (IVDD) is a complex pathological condition associated with the development of low back pain. Despite numerous studies, the specific molecular mechanisms underlying IVDD remain unclear. At the cellular level, IVDD involves a series of changes, including cell proliferation, cell death, and inflammation. Of these, cell death plays a critical role in the progression of the condition. In recent years, necroptosis has been identified as a new form of programmed cell death (PCD). Necroptosis can be activated by ligands of death receptors, which then interact with RIPK1, RIPK3 and MLKL and lead to necrosome formation.. According to various previous studies, the necroptosis related pathway is activated in IVDD, and plays a significant role in the pathogenesis of IVDD. Furthermore, necroptosis may serve as a target for the IVDD treatment. Recently, several studies have reported the role of necroptosis in IVDD, but few studies have summarized the association between IVDD and necroptosis. The review gives a brief summary of the research progress of necroptosis, and discusses strategies and mechanisms that target necroptosis in IVDD. Lastly, matters needing attention in the necroptosis targeted therapy of IVDD are put forward at last. To the best of our knowledge, the review paper is the first one that integrates current research about the impact of necroptosis on IVDD, and contributes to the future therapy of IVDD from new perspectives.

Keywords: Cell death; Intervertebral disc degeneration; Necroptosis; Nucleus pulposus.