Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730000, China.
Affiliated Hospital of Xizang Minzu University, Xianyang 712082, China.
Biomolecules. 2022 Aug 4;12(8):1074. doi: 10.3390/biom12081074.
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.
椎间盘退变性疾病(IVDD)是一种全球范围内常见的肌肉骨骼退行性疾病,其主要临床表现为腰痛(LBP);大约 80%的人在其一生中会受到影响。目前,IVDD 的发病机制尚不清楚,现代治疗方法只能缓解其症状,但不能抑制或逆转其进展。然而,近年来,靶向治疗带来了新的治疗策略。含半胱氨酸的天冬氨酸蛋白酶(caspases)是一种存在于细胞质中的蛋白酶家族。它们在进化上是保守的,参与真核细胞的生长、分化和凋亡死亡。近年来,它被证实参与了各种疾病的发病机制,主要通过调节细胞凋亡和炎症反应。随着对 IVDD 发病机制和病理过程的不断研究,越来越多的研究表明 caspases 与 IVDD 过程密切相关,特别是在椎间盘(IVD)细胞凋亡和炎症反应中。因此,本文我们就 caspases 在 IVDD 中的作用进行研究,涉及 caspases 的结构和相关信号通路。这将有助于探索调节相关 caspases 活性的策略,并开发 caspase 抑制剂来预防和治疗 IVDD。本综述的目的是确定参与 IVDD 的 caspases,它们可能是治疗 IVDD 的潜在靶点。