Dzurová Lenka, Holásková Edita, Pospíšilová Hana, Schneider Rauber Gabriela, Frébortová Jitka
Czech Advanced Technology and Research Institute (CATRIN), Palacký University Olomouc, 77900 Olomouc, Czech Republic.
Antibiotics (Basel). 2024 Dec 24;14(1):1. doi: 10.3390/antibiotics14010001.
Cathelicidins are a group of cationic, amphipathic peptides that play a vital role in the innate immune response of many vertebrates, including humans. Produced by immune and epithelial cells, they serve as natural defenses against a wide range of pathogens, including bacteria, viruses, and fungi. In humans, the cathelicidin LL-37 is essential for wound healing, maintaining skin barrier integrity, and combating infections. Cathelicidins of different origins have shown potential in treating various skin conditions, including melanoma, acne, and diabetic foot ulcers. Despite their promising therapeutic potential, cathelicidins face significant challenges in clinical application. Many peptide-based therapies have failed in clinical trials due to unclear efficacy and safety concerns. Additionally, the emergence of bacterial resistance, which contradicts initial claims of non-resistance, further complicates their development. To successfully translate cathelicidins into effective clinical treatments, therefore, several obstacles must be addressed, including a better understanding of their mechanisms of action, sustainable large-scale production, optimized formulations for drug delivery and stability, and strategies to overcome microbial resistance. This review examines the current knowledge of cathelicidins and their therapeutic applications and discusses the challenges that hinder their clinical use and must be overcome to fully exploit their potential in medicine.
cathelicidin抗菌肽是一类阳离子两亲性肽，在包括人类在内的许多脊椎动物的先天免疫反应中发挥着至关重要的作用。它们由免疫细胞和上皮细胞产生，作为抵御多种病原体（包括细菌、病毒和真菌）的天然防御物质。在人类中，cathelicidin抗菌肽LL-37对伤口愈合、维持皮肤屏障完整性和对抗感染至关重要。不同来源的cathelicidin抗菌肽在治疗各种皮肤疾病（包括黑色素瘤、痤疮和糖尿病足溃疡）方面已显示出潜力。尽管它们具有广阔的治疗潜力，但cathelicidin抗菌肽在临床应用中面临重大挑战。许多基于肽的疗法由于疗效不明确和安全性问题在临床试验中失败。此外，细菌耐药性的出现与最初声称的无耐药性相矛盾，进一步使它们的开发复杂化。因此，为了成功地将cathelicidin抗菌肽转化为有效的临床治疗方法，必须解决几个障碍，包括更好地了解它们的作用机制、可持续的大规模生产、优化药物递送和稳定性的配方，以及克服微生物耐药性的策略。这篇综述探讨了目前关于cathelicidin抗菌肽及其治疗应用的知识，并讨论了阻碍其临床应用的挑战，以及为充分发挥其在医学上的潜力必须克服的问题。
