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非编码 RNA 在重症肌无力中的作用:从免疫调节到个体化医疗。

Non-Coding RNAs in Myasthenia Gravis: From Immune Regulation to Personalized Medicine.

机构信息

Neurology 4-Neuroimmunology and Neuromuscolar Diseases, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy.

Ph.D. Program in Neuroscience, University of Milano-Bicocca, 20900 Monza, Italy.

出版信息

Cells. 2024 Sep 14;13(18):1550. doi: 10.3390/cells13181550.

Abstract

Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder characterized by altered neuromuscular transmission, which causes weakness and fatigability in the skeletal muscles. The etiology of MG is complex, being associated with multiple genetic and environmental factors. Over recent years, progress has been made in understanding the immunological alterations implicated in the disease, but the exact pathogenesis still needs to be elucidated. A pathogenic interplay between innate immunity and autoimmunity contributes to the intra-thymic MG development. Epigenetic changes are critically involved in both innate and adaptive immune response regulation. They can act as (i) pathological factors besides genetic predisposition and (ii) co-factors contributing to disease phenotypes or patient-specific disease course/outcomes. This article reviews the role of non-coding RNAs (ncRNAs) as epigenetic factors implicated in MG. Particular attention is dedicated to microRNAs (miRNAs), whose expression is altered in MG patients' thymuses and circulating blood. The long ncRNA (lncRNA) contribution to MG, although not fully characterized yet, is also discussed. By summarizing the most recent and fast-growing findings on ncRNAs in MG, we highlight the therapeutic potential of these molecules for achieving immune regulation and their value as biomarkers for the development of personalized medicine approaches to improve disease care.

摘要

重症肌无力(MG)是一种抗体介导的自身免疫性疾病,其特征是神经肌肉传递发生改变,导致骨骼肌无力和易疲劳。MG 的病因复杂,与多种遗传和环境因素有关。近年来,人们在理解疾病相关的免疫学改变方面取得了进展,但确切的发病机制仍需阐明。先天免疫和自身免疫之间的致病相互作用导致了胸腺内 MG 的发展。表观遗传变化在先天和适应性免疫反应的调节中起着关键作用。它们可以作为(i)除遗传易感性之外的病理因素,以及(ii)导致疾病表型或患者特异性疾病过程/结果的共同因素。本文综述了非编码 RNA(ncRNA)作为与 MG 相关的表观遗传因素的作用。特别关注 microRNAs(miRNAs),其在 MG 患者的胸腺和循环血液中的表达发生改变。尽管长 ncRNA(lncRNA)在 MG 中的作用尚未完全阐明,但也进行了讨论。通过总结 MG 中 ncRNA 的最新和快速发展的研究结果,我们强调了这些分子在实现免疫调节方面的治疗潜力,以及它们作为生物标志物在开发个性化医疗方法以改善疾病治疗方面的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c7ae/11430632/d847a95c0dbb/cells-13-01550-g001.jpg

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