Role of Caspase Family in Intervertebral Disc Degeneration and Its Therapeutic Prospects

Abstract

Intervertebral disc degeneration (IVDD) is a common musculoskeletal degenerative disease worldwide, of which the main clinical manifestation is low back pain (LBP); approximately, 80% of people suffer from it in their lifetime. Currently, the pathogenesis of IVDD is unclear, and modern treatments can only alleviate its symptoms but cannot inhibit or reverse its progression. However, in recent years, targeted therapy has led to new therapeutic strategies. Cysteine-containing aspartate proteolytic enzymes (caspases) are a family of proteases present in the cytoplasm. They are evolutionarily conserved and are involved in cell growth, differentiation, and apoptotic death of eukaryotic cells. In recent years, it has been confirmed to be involved in the pathogenesis of various diseases, mainly by regulating cell apoptosis and inflammatory response. With continuous research on the pathogenesis and pathological process of IVDD, an increasing number of studies have shown that caspases are closely related to the IVDD process, especially in the intervertebral disc (IVD) cell apoptosis and inflammatory response. Therefore, herein we study the role of caspases in IVDD with respect to the structure of caspases and the related signaling pathways involved. This would help explore the strategy of regulating the activity of the caspases involved and develop caspase inhibitors to prevent and treat IVDD. The aim of this review was to identify the caspases involved in IVDD which could be potential targets for the treatment of IVDD.

Keywords: apoptosis; caspase; inflammation; inhibitor; intervertebral disc degeneration.

Figure 1

Classification, functions and the basic structure of caspase family: h, human; m, mouse; b, bovine.

Figure 2

Potential mechanism of caspase involved in apoptosis of IVD cells. DISC, Death-inducing signaling complex; IVD, Intervertebral disc; ERS, Endoplasmic reticulum stress; ROS, Reactive oxygen species; MMOP, Mitochondrial outer membrane permeabilization; RE, Recruit.

Figure 3

Caspase may be involved in the mechanism of inflammatory response in IVDD. GSDMD, Gasdermin D; GASDMD-N, Gasdermin D N terminal; GASDMD-C, Gasdermin D C terminal.