Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani, India.
Department of Pharmacy, Milestones Institute of Pharmaceutical Sciences, Udaipur, Tripura, India.
Expert Opin Ther Targets. 2024 Aug;28(8):689-700. doi: 10.1080/14728222.2024.2387604. Epub 2024 Aug 5.
Psoriasis is a chronic immune-mediated disorder affecting over 2-3% of the population worldwide, significantly impacting quality of life. Despite the availability of various therapeutic interventions, concerns persist regarding lesion recurrence and potential alterations in immune surveillance promoting cancer progression. Recent advancements in understanding cellular and molecular pathways have unveiled key factors in psoriasis etiology, including IL-17, 22, 23, TNF-α, PDE-4, JAK-STAT inhibitors, and AhR agonists. This work explores the potential of S-phase kinase-associated protein 2 (Skp2) as a therapeutic target in psoriasis.
This review covers the current understanding of psoriasis pathophysiology, including immune dysregulation, and the role of keratinocytes and ubiquitin. It also delves into Skp2 role in cell cycle regulation, and its correlation with angiogenesis and ubiquitin in psoriasis. The evolving therapeutic approaches targeting Skp2, including small molecule inhibitors, are also discussed.
Targeting Skp2 holds promise for developing novel therapeutic approaches for psoriasis. By modulating Skp2 activity or expression, it may be possible to intervene in inflammatory and proliferative processes underlying the disease. Further research into Skp2 inhibitors and their efficacy in preclinical and clinical settings is warranted to harness the full potential of Skp2 as a therapeutic target in psoriasis management.
银屑病是一种影响全球超过 2-3%人口的慢性免疫介导性疾病,严重影响生活质量。尽管有多种治疗干预措施,但仍存在对病变复发和潜在免疫监视改变促进癌症进展的担忧。对细胞和分子途径的理解的最新进展揭示了银屑病发病机制中的关键因素,包括 IL-17、22、23、TNF-α、PDE-4、JAK-STAT 抑制剂和 AhR 激动剂。这项工作探讨了 S 期激酶相关蛋白 2 (Skp2) 作为银屑病治疗靶点的潜力。
本综述涵盖了对银屑病发病机制的现有理解,包括免疫失调以及角质形成细胞和泛素的作用。它还深入探讨了 Skp2 在细胞周期调控中的作用,以及它与银屑病中血管生成和泛素的相关性。还讨论了针对 Skp2 的新兴治疗方法,包括小分子抑制剂。
靶向 Skp2 为开发银屑病的新型治疗方法提供了希望。通过调节 Skp2 的活性或表达,可能有可能干预疾病潜在的炎症和增殖过程。需要进一步研究 Skp2 抑制剂及其在临床前和临床环境中的疗效,以充分发挥 Skp2 作为银屑病治疗靶点的潜力。