Stauffer Winston T, Goodman Asha Z, Gallay Philippe A
Department of Immunology & Microbiology, The Scripps Research Institute, La Jolla, CA, United States.
Front Pharmacol. 2024 Jul 8;15:1417945. doi: 10.3389/fphar.2024.1417945. eCollection 2024.
Cyclophilins (Cyps), characterized as peptidyl-prolyl isomerases (PPIases), are highly conserved and ubiquitous, playing a crucial role in protein folding and cellular signaling. This review summarizes the biochemical pathways mediated by Cyps, including their involvement in pathological states such as viral replication, inflammation, and cancer progression, to underscore the therapeutic potential of Cyp inhibition. The exploration of Cyp inhibitors (CypI) in this review, particularly non-immunosuppressive cyclosporine A (CsA) derivatives, highlights their significance as therapeutic agents. The structural and functional nuances of CsA derivatives are examined, including their efficacy, mechanism of action, and the balance between therapeutic benefits and off-target effects. The landscape of CypI is evaluated to emphasize the clinical need for targeted approaches to exploit the complex biology of Cyps and to propose future directions for research that may enhance the utility of non-immunosuppressive CsA derivatives in treating diseases where Cyps play a key pathological role.
亲环蛋白（Cyps）被表征为肽基脯氨酰异构酶（PPIases），具有高度保守性且广泛存在，在蛋白质折叠和细胞信号传导中发挥着关键作用。本综述总结了亲环蛋白介导的生化途径，包括它们在病毒复制、炎症和癌症进展等病理状态中的作用，以强调抑制亲环蛋白的治疗潜力。本综述对亲环蛋白抑制剂（CypI）的探索，特别是非免疫抑制性环孢素A（CsA）衍生物，突出了它们作为治疗药物的重要性。研究了CsA衍生物的结构和功能细微差别，包括它们的疗效、作用机制以及治疗益处与脱靶效应之间的平衡。评估了亲环蛋白抑制剂的前景，以强调针对亲环蛋白复杂生物学特性的靶向方法的临床需求，并为未来的研究提出方向，这些研究可能会提高非免疫抑制性CsA衍生物在治疗亲环蛋白起关键病理作用的疾病中的效用。
