Department of Pediatrics, PICU, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Department of Pediatrics, PICU, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Pharmacol Res. 2024 Oct;208:107410. doi: 10.1016/j.phrs.2024.107410. Epub 2024 Sep 12.
Histone deacetylases (HDACs) are zinc-dependent deacetylases that remove acetyl groups from lysine residues of histones or form protein complexes with other proteins for transcriptional repression, changing chromatin structure tightness, and inhibiting gene expression. Recent in vivo and in vitro studies have amply demonstrated the critical role of HDACs in the cell biology of the nervous system during both physiological and pathological processes and have provided new insights into the conduct of research on neurological disease targets. In addition, in vitro and in vivo studies on HDAC inhibitors show promise for the treatment of various diseases. This review summarizes the regulatory mechanisms of HDAC and the important role of its downstream targets in nervous system diseases, and summarizes the therapeutic mechanisms and efficacy of HDAC inhibitors in various nervous system diseases. Additionally, the current pharmacological situation, problems, and developmental prospects of HDAC inhibitors are described. A better understanding of the pathogenic mechanisms of HDACs in the nervous system may reveal new targets for therapeutic interventions in diseases and help to relieve healthcare pressure through preventive measures.
组蛋白去乙酰化酶（HDACs）是锌依赖性去乙酰化酶，可从组蛋白赖氨酸残基上去除乙酰基，或与其他蛋白质形成蛋白复合物，发挥转录抑制作用，改变染色质结构的紧密程度，抑制基因表达。近期的体内和体外研究充分证明了 HDACs 在生理和病理过程中对神经系统细胞生物学的关键作用，并为神经疾病靶点的研究提供了新的见解。此外，HDAC 抑制剂的体内和体外研究显示出在治疗各种疾病方面的广阔前景。本综述总结了 HDAC 的调控机制及其下游靶标在神经系统疾病中的重要作用，并总结了 HDAC 抑制剂在各种神经系统疾病中的治疗机制和疗效。此外，还描述了 HDAC 抑制剂的当前药理学状况、问题和发展前景。更好地了解 HDACs 在神经系统中的致病机制可能会为疾病的治疗干预提供新的靶点，并通过预防措施帮助缓解医疗保健压力。
