<br>LL-37：结构、抗菌活性和对淀粉样蛋白相关疾病的影响,Biomolecules

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LL-37：结构、抗菌活性和对淀粉样蛋白相关疾病的影响
Biomolecules ( IF 4.8 ) Pub Date : 2024-03-08 , DOI: 10.3390/biom14030320
Surajit Bhattacharjya ₁ , Zhizhuo Zhang ₂ , Ayyalusamy Ramamoorthy _{2,

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Affiliation

抗菌肽（AMP）以及宿主防御肽（HDP）构成了先天免疫系统的第一道防线。已知人类表达抗菌前体蛋白，这些前体蛋白经过进一步加工以产生 AMP，包括几种类型的 α/β 防御素、组抑素和猫咪杀素衍生的 AMP，如 LL37。AMP 的广谱活性对于防御病原菌、病毒、真菌和寄生虫引起的感染至关重要。多重耐药病原菌的出现引起了全球公共卫生的关注。用 AMPs 靶向抗生素耐药菌株的前景对于开发新一代抗菌剂具有重要意义。37 个残基长的 LL37 是人类中唯一的 cathelicidin 家族 AMP，一直是过去几十年研究的主要焦点。LL37 的宿主防御活性可能通过其在全身的表达来强调，从各种器官（睾丸、皮肤、呼吸道和胃肠道）的上皮细胞到免疫细胞。值得注意的是，除了经典直接杀死病原微生物外，LL37 还发挥其他几种宿主防御活性，包括炎症反应调节、化疗吸引以及感染部位的伤口愈合和闭合。此外，LL37 及其衍生肽具有抗癌和抗淀粉样蛋白生成特性。在这篇综述文章中，我们旨在基于近年来已知的生物物理、结构和功能研究，对 LL37 及其衍生肽进行综合、机械性的见解。我们相信，本文将为未来基于 LL37 的新型分子的结构、生化和生物物理性质以及设计的研究铺平道路。

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LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases

Antimicrobial peptides (AMPs), as well as host defense peptides (HDPs), constitute the first line of defense as part of the innate immune system. Humans are known to express antimicrobial precursor proteins, which are further processed to generate AMPs, including several types of α/β defensins, histatins, and cathelicidin-derived AMPs like LL37. The broad-spectrum activity of AMPs is crucial to defend against infections caused by pathogenic bacteria, viruses, fungi, and parasites. The emergence of multi-drug resistant pathogenic bacteria is of global concern for public health. The prospects of targeting antibiotic-resistant strains of bacteria with AMPs are of high significance for developing new generations of antimicrobial agents. The 37-residue long LL37, the only cathelicidin family of AMP in humans, has been the major focus for the past few decades of research. The host defense activity of LL37 is likely underscored by its expression throughout the body, spanning from the epithelial cells of various organs—testis, skin, respiratory tract, and gastrointestinal tract—to immune cells. Remarkably, apart from canonical direct killing of pathogenic organisms, LL37 exerts several other host defense activities, including inflammatory response modulation, chemo-attraction, and wound healing and closure at the infected sites. In addition, LL37 and its derived peptides are bestowed with anti-cancer and anti-amyloidogenic properties. In this review article, we aim to develop integrative, mechanistic insight into LL37 and its derived peptides, based on the known biophysical, structural, and functional studies in recent years. We believe that this review will pave the way for future research on the structures, biochemical and biophysical properties, and design of novel LL37-based molecules.

更新日期：2024-03-08

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