Suppr超能文献

组蛋白乙酰转移酶和组蛋白去乙酰化酶:在神经退行性疾病中具有相反作用的酶

HAT and HDAC: Enzyme with Contradictory Action in Neurodegenerative Diseases.

作者信息

Singh Richa, Rathore Aaina Singh, Dilnashin Hagera, Keshri Priyanka Kumari, Gupta Nitesh Kumar, Prakash Singh Ankit Satya, Zahra Walia, Singh Shekhar, Singh Surya Pratap

机构信息

Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi-221005 (U.P.), India.

出版信息

Mol Neurobiol. 2024 Nov;61(11):9110-9124. doi: 10.1007/s12035-024-04115-6. Epub 2024 Apr 8.

Abstract

In view of the increasing risk of neurodegenerative diseases, epigenetics plays a fundamental role in the field of neuroscience. Several modifications have been studied including DNA methylation, histone acetylation, histone phosphorylation, etc. Histone acetylation and deacetylation regulate gene expression, and the regular activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs) provides regulatory stages for gene expression and cell cycle. Imbalanced homeostasis in these enzymes causes a detrimental effect on neurophysiological function. Intriguingly, epigenetic remodelling via histone acetylation in certain brain areas has been found to play a key role in the neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. It has been demonstrated that a number of HATs have a role in crucial brain processes such regulating neuronal plasticity and memory formation. The most recent therapeutic methods involve the use of small molecules known as histone deacetylase (HDAC) inhibitors that antagonize HDAC activity thereby increase acetylation levels in order to prevent the loss of HAT function in neurodegenerative disorders. The target specificity of the HDAC inhibitors now in use raises concerns about their applicability, despite the fact that this strategy has demonstrated promising therapeutic outcomes. The aim of this review is to summarize the cross-linking between histone modification and its regulation in the pathogenesis of neurological disorders. Furthermore, these findings also support the notion of new pharmacotherapies that target particular areas of the brain using histone deacetylase inhibitors.

摘要

鉴于神经退行性疾病的风险不断增加,表观遗传学在神经科学领域发挥着重要作用。人们已经研究了多种修饰,包括DNA甲基化、组蛋白乙酰化、组蛋白磷酸化等。组蛋白乙酰化和去乙酰化调节基因表达,组蛋白乙酰转移酶(HATs)和组蛋白去乙酰化酶(HDACs)的正常活性为基因表达和细胞周期提供了调控阶段。这些酶的体内平衡失衡会对神经生理功能产生有害影响。有趣的是,在某些脑区通过组蛋白乙酰化进行的表观遗传重塑已被发现,在阿尔茨海默病、帕金森病和亨廷顿病等神经退行性疾病中起关键作用。已经证明,许多HATs在调节神经元可塑性和记忆形成等关键脑过程中发挥作用。最新的治疗方法包括使用称为组蛋白去乙酰化酶(HDAC)抑制剂的小分子,这些抑制剂可拮抗HDAC活性,从而提高乙酰化水平,以防止神经退行性疾病中HAT功能的丧失。尽管这一策略已显示出有前景的治疗效果,但目前使用的HDAC抑制剂的靶点特异性引发了对其适用性的担忧。本综述的目的是总结组蛋白修饰及其调控在神经疾病发病机制中的交联作用。此外,这些发现还支持了使用组蛋白去乙酰化酶抑制剂靶向大脑特定区域的新药物疗法的观点。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验