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炎症性疾病中组蛋白和非组蛋白的去乙酰化以及组蛋白去乙酰化酶抑制剂的癌症治疗潜力

Deacetylation of Histones and Non-histone Proteins in Inflammatory Diseases and Cancer Therapeutic Potential of Histone Deacetylase Inhibitors.

作者信息

Man Ezgi, Evran Serap

机构信息

Department of Biochemistry, Faculty of Science, Ege University, 35100, İzmir, Türkiye.

EGE SCIENCE PRO Scientific Research Inc., Ege University, IdeEGE Technology Development Zone, 35100, Bornova-Izmir, Türkiye.

出版信息

Curr Genomics. 2023 Nov 22;24(3):136-145. doi: 10.2174/0113892029265046231011100327.

Abstract

Epigenetic changes play an important role in the pathophysiology of autoimmune diseases such as allergic asthma, multiple sclerosis, lung diseases, diabetes, cystic fibrosis, atherosclerosis, rheumatoid arthritis, and COVID-19. There are three main classes of epigenetic alterations: post-translational modifications of histone proteins, control by non-coding RNA and DNA methylation. Since histone modifications can directly affect chromatin structure and accessibility, they can regulate gene expression levels. Abnormal expression and activity of histone deacetylases (HDACs) have been reported in immune mediated diseases. Increased acetylated levels of lysine residues have been suggested to be related to the overexpression of inflammatory genes. This review focuses on the effect of HDAC modifications on histone and non-histone proteins in autoimmune diseases. Furthermore, we discuss the potential therapeutic effect of HDAC inhibitors (HDACi) used in these diseases.

摘要

表观遗传变化在自身免疫性疾病的病理生理学中起着重要作用,如过敏性哮喘、多发性硬化症、肺部疾病、糖尿病、囊性纤维化、动脉粥样硬化、类风湿性关节炎和新冠肺炎。表观遗传改变主要有三类:组蛋白的翻译后修饰、非编码RNA的调控和DNA甲基化。由于组蛋白修饰可直接影响染色质结构和可及性,因此它们能够调节基因表达水平。在免疫介导的疾病中,已有报道称组蛋白去乙酰化酶(HDAC)的表达和活性异常。赖氨酸残基乙酰化水平升高被认为与炎症基因的过表达有关。本综述重点关注HDAC修饰对自身免疫性疾病中组蛋白和非组蛋白的影响。此外,我们还讨论了这些疾病中使用的HDAC抑制剂(HDACi)的潜在治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92d2/10761333/fc074c6a5fe3/CG-24-136_F1.jpg

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