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哮喘糖基化模式的研究进展:如何通过改变固有途径开发新疗法。

The Exploitation of the Glycosylation Pattern in Asthma: How We Alter Ancestral Pathways to Develop New Treatments.

机构信息

Molecure S.A., Zwirki i Wigury 101, 02-089 Warszawa, Poland.

出版信息

Biomolecules. 2024 Apr 24;14(5):513. doi: 10.3390/biom14050513.

Abstract

Asthma has reached epidemic levels, yet progress in developing specific therapies is slow. One of the main reasons for this is the fact that asthma is an umbrella term for various distinct subsets. Due to its high heterogeneity, it is difficult to establish biomarkers for each subset of asthma and to propose endotype-specific treatments. This review focuses on protein glycosylation as a process activated in asthma and ways to utilize it to develop novel biomarkers and treatments. We discuss known and relevant glycoproteins whose functions control disease development. The key role of glycoproteins in processes integral to asthma, such as inflammation, tissue remodeling, and repair, justifies our interest and research in the field of glycobiology. Altering the glycosylation states of proteins contributing to asthma can change the pathological processes that we previously failed to inhibit. Special emphasis is placed on chitotriosidase 1 (CHIT1), an enzyme capable of modifying LacNAc- and LacdiNAc-containing glycans. The expression and activity of CHIT1 are induced in human diseased lungs, and its pathological role has been demonstrated by both genetic and pharmacological approaches. We propose that studying the glycosylation pattern and enzymes involved in glycosylation in asthma can help in patient stratification and in developing personalized treatment.

摘要

哮喘已达到流行水平,但开发特定疗法的进展缓慢。其中一个主要原因是哮喘是各种不同亚群的总称。由于其高度异质性,很难为哮喘的每个亚群建立生物标志物,并提出针对特定表型的治疗方法。本综述重点关注蛋白质糖基化作为哮喘中激活的一个过程,以及利用它开发新型生物标志物和治疗方法的方法。我们讨论了已知和相关的糖蛋白,其功能控制疾病的发展。糖蛋白在哮喘的炎症、组织重塑和修复等重要过程中起着关键作用,这证明了我们对糖生物学领域的兴趣和研究。改变参与哮喘的蛋白质的糖基化状态可以改变我们以前未能抑制的病理过程。特别强调的是几丁质酶 1(CHIT1),它是一种能够修饰含有 LacNAc 和 LacdiNAc 的聚糖的酶。CHIT1 在人患病肺部中的表达和活性被诱导,其病理作用已通过遗传和药理学方法得到证实。我们提出,研究哮喘中糖基化模式和参与糖基化的酶可以帮助进行患者分层和开发个性化治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d49/11117584/de9f0f8fbe1a/biomolecules-14-00513-g001.jpg

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