Chitkara College of Pharmacy, Chitkara University, 140401 Punjab, India.
Department of Pharmacology, Central University of Punjab, Ghudda, Bathinda, India.
Int Immunopharmacol. 2022 Sep;110:108951. doi: 10.1016/j.intimp.2022.108951. Epub 2022 Jun 16.
Caspases are intimately associated with altering various signaling pathways, resulting in programmed cell death or apoptosis. Apoptosis is necessary for the normal homeostasis of cells and their development. The untoward activation of apoptotic pathways indirectly or directly results in pathologies of various diseases. Identifying different caspases in apoptotic pathways directed the research to develop caspase inhibitors as therapeutic agents. However, no drug is available in the market that targets caspase inhibition and produces a therapeutic effect. Here, we will shed light on the role of caspases in the number of neuronal disorders and neurodegenerative diseases. The article reviews the findings about the activation of various upstream mechanisms associated with caspases in neurodegenerative disorders along with the recent progress in the generation of caspase inhibitors and the challenge faced in their development as therapeutic agents for neurological indications.
Caspases 与改变各种信号通路密切相关，导致程序性细胞死亡或细胞凋亡。细胞凋亡对于细胞的正常内稳态及其发育是必要的。凋亡途径的意外激活间接或直接导致各种疾病的病理变化。鉴定凋亡途径中的不同半胱天冬酶促使研究人员开发半胱天冬酶抑制剂作为治疗剂。然而，目前市场上没有针对半胱天冬酶抑制作用并产生治疗效果的药物。在这里，我们将阐明半胱天冬酶在多种神经障碍和神经退行性疾病中的作用。本文综述了关于神经退行性疾病中与半胱天冬酶相关的各种上游机制的激活的研究结果，以及半胱天冬酶抑制剂的最新进展，以及作为治疗神经适应症的治疗剂开发所面临的挑战。
