Abdelghany Lina, Sillapachaiyaporn Chanin, Zhivotovsky Boris
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, SE-171 77, Sweden.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt.
Cell Mol Life Sci. 2024 Dec 3;81(1):474. doi: 10.1007/s00018-024-05495-7.
Since the late 20th century, researchers have known that caspases are a pillar of cell death, particularly apoptosis. However, recent advances in cell biology have unraveled the multiple roles of caspases. These enzymes have an unconventional role in cell proliferation, differentiation, and invasion. As a result, caspase deregulation can fuel the fire of cancer, incite flames of inflammation, flare neurodegenerative disorders, and exacerbate skin pathologies. Several therapeutic approaches toward caspase inhibition have been investigated, but can caspase inhibitors harness the maladaptive effect of these proteases without causing significant side effects? A few studies have exploited caspase induction for cancer or adoptive cell therapies. Here, we provide a compelling picture of caspases, starting with their evolution, their polytomous roles beyond cell death, the flaws of their deregulation, and the merits of targeting them for therapeutic implications. Furthermore, we provide a deeper understanding of the evolution of caspase-related research up to the current era, pinpointing the role of caspases in cell survival and aiding in the development of effective caspase-targeted therapies.
自20世纪末以来，研究人员就已经知道半胱天冬酶是细胞死亡尤其是细胞凋亡的一个支柱。然而，细胞生物学的最新进展揭示了半胱天冬酶的多种作用。这些酶在细胞增殖、分化和侵袭中具有非传统作用。因此，半胱天冬酶失调会助长癌症之火、引发炎症之火、加剧神经退行性疾病并加重皮肤病变。已经研究了几种针对半胱天冬酶抑制的治疗方法，但是半胱天冬酶抑制剂能否在不引起显著副作用的情况下利用这些蛋白酶的适应不良效应呢？一些研究已经利用半胱天冬酶诱导进行癌症治疗或过继性细胞疗法。在这里，我们对半胱天冬酶进行了全面的描述，从它们的进化、细胞死亡之外的多方面作用、失调的缺陷以及针对它们进行治疗的意义等方面展开。此外，我们对直至当前时代半胱天冬酶相关研究的进展有了更深入的理解，明确了半胱天冬酶在细胞存活中的作用，并有助于开发有效的靶向半胱天冬酶的疗法。
