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组蛋白去乙酰化酶抑制剂在非肿瘤性疾病中的作用。

Role of histone deacetylase inhibitors in non-neoplastic diseases.

作者信息

Zhou Chunxiao, Zhao Dengke, Wu Chunyan, Wu Zhimin, Zhang Wen, Chen Shilv, Zhao Xindong, Wu Shaoling

机构信息

College of Medicine, Qingdao University, Qingdao, 266000, China.

Harbin Medical University, Harbin, 150000, China.

出版信息

Heliyon. 2024 Jul 2;10(13):e33997. doi: 10.1016/j.heliyon.2024.e33997. eCollection 2024 Jul 15.

Abstract

BACKGROUND

Epigenetic dysregulation has been implicated in the development and progression of a variety of human diseases, but epigenetic changes are reversible, and epigenetic enzymes and regulatory proteins can be targeted using small molecules. Histone deacetylase inhibitors (HDACis), as a class of epigenetic drugs, are widely used to treat various cancers and other diseases involving abnormal gene expression.

RESULTS

Specially, HDACis have emerged as a promising strategy to enhance the therapeutic effect of non-neoplastic conditions, including neurological disorders, cardiovascular diseases, renal diseases, autoimmune diseases, inflammatory diseases, infectious diseases and rare diseases, along with their related mechanisms. However, their clinical efficacy has been limited by drug resistance and toxicity.

CONCLUSIONS

To date, most clinical trials of HDAC inhibitors have been related to the treatment of cancer rather than the treatment of non-cancer diseases, for which experimental studies are gradually underway. Discussions regarding non-neoplastic diseases often concentrate on specific disease types. Therefore, this review highlights the development of HDACis and their potential therapeutic applications in non-neoplastic diseases, either as monotherapy or in combination with other drugs or therapies.

摘要

背景

表观遗传失调与多种人类疾病的发生和发展有关,但表观遗传变化是可逆的,并且可以使用小分子靶向表观遗传酶和调节蛋白。组蛋白去乙酰化酶抑制剂(HDACis)作为一类表观遗传药物,被广泛用于治疗各种癌症和其他涉及异常基因表达的疾病。

结果

特别地,HDACis已成为增强非肿瘤性疾病治疗效果的一种有前景的策略,这些疾病包括神经疾病、心血管疾病、肾脏疾病、自身免疫性疾病、炎症性疾病、感染性疾病和罕见疾病,以及它们的相关机制。然而,它们的临床疗效受到耐药性和毒性的限制。

结论

迄今为止,大多数HDAC抑制剂的临床试验都与癌症治疗有关,而非癌症疾病的治疗则逐渐开展实验研究。关于非肿瘤性疾病的讨论通常集中在特定疾病类型上。因此,本综述重点介绍了HDACis的发展及其在非肿瘤性疾病中的潜在治疗应用,无论是作为单一疗法还是与其他药物或疗法联合使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f47f/11283006/346139b14ec3/gr1.jpg

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