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风湿学中的表观遗传学革命:组蛋白去乙酰化酶抑制剂在靶向类风湿关节炎干预中的潜力。

Epi-revolution in rheumatology: the potential of histone deacetylase inhibitors for targeted rheumatoid arthritis intervention.

机构信息

Department of Biophysics, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.

Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.

出版信息

Inflammopharmacology. 2024 Aug;32(4):2109-2123. doi: 10.1007/s10787-024-01486-z. Epub 2024 May 7.

Abstract

Autoimmune diseases hold significant importance in the realm of medical research, prompting a thorough exploration of potential therapeutic interventions. One crucial aspect of this exploration involves understanding the intricate processes of histone acetylation and deacetylation. Histone acetylation, facilitated by histone acetyl transferases (HATs), is instrumental in rendering DNA transcriptionally active. Conversely, histone deacetylases (HDACs) are responsible for the removal of acetyl groups, influencing gene expression regulation. The upregulation of HDACs, observed in various cancers, has steered attention towards histone deacetylase inhibitors (HDACi) as promising anti-cancer agents. Beyond cancer, HDACi has demonstrated anti-inflammatory properties, prompting interest in their potential therapeutic applications for inflammatory diseases such as rheumatoid arthritis (RA). RA, characterized by the immune system erroneously attacking healthy cells, leads to joint inflammation. Recent studies suggest that HDACi could offer a viable therapeutic strategy for RA, with potential mechanisms including the inhibition of synovial tissue growth and suppression of pro-inflammatory cytokines. Furthermore, HDACi may exert protective effects on bone and cartilage, common targets in RA pathology. In-depth investigations through in vivo and histopathology studies contribute to the ongoing discourse on the therapeutic benefits of HDACis in the context of RA treatment.

摘要

自身免疫性疾病在医学研究领域具有重要意义,促使人们深入探索潜在的治疗干预措施。在探索过程中,一个关键方面涉及理解组蛋白乙酰化和去乙酰化的复杂过程。组蛋白乙酰转移酶(HATs)介导的组蛋白乙酰化有助于使 DNA 转录活跃。相反,组蛋白去乙酰化酶(HDACs)负责去除乙酰基,影响基因表达调控。在各种癌症中观察到的 HDACs 上调引起了人们对组蛋白去乙酰化酶抑制剂(HDACi)作为有前途的抗癌药物的关注。除了癌症,HDACi 还具有抗炎特性,这促使人们对其在类风湿关节炎(RA)等炎症性疾病中的潜在治疗应用产生了兴趣。RA 是免疫系统错误攻击健康细胞导致关节炎症的疾病。最近的研究表明,HDACi 可能为 RA 提供一种可行的治疗策略,其潜在机制包括抑制滑膜组织生长和抑制促炎细胞因子。此外,HDACi 可能对骨和软骨产生保护作用,RA 病理中常见的靶标。通过体内和组织病理学研究的深入调查,有助于在 RA 治疗背景下探讨 HDACi 的治疗益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/719f/11300544/13d0bbff27ae/10787_2024_1486_Fig1_HTML.jpg

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