Shukla Surabhi, Tekwani Babu L
Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL, United States.
Division of Drug Discovery, Department of Infectious Diseases, Southern Research, Birmingham, AL, United States.
Front Pharmacol. 2020 Apr 24;11:537. doi: 10.3389/fphar.2020.00537. eCollection 2020.
Histone deacetylases (HADC) are the enzymes that remove acetyl group from lysine residue of histones and non-histone proteins and regulate the process of transcription by binding to transcription factors and regulating fundamental cellular process such as cellular proliferation, differentiation and development. In neurodegenerative diseases, the histone acetylation homeostasis is greatly impaired, shifting towards a state of hypoacetylation. The histone hyperacetylation produced by direct inhibition of HDACs leads to neuroprotective actions. This review attempts to elaborate on role of small molecule inhibitors of HDACs on neuronal differentiation and throws light on the potential of HDAC inhibitors as therapeutic agents for treatment of neurodegenerative diseases. The role of HDACs in neuronal cellular and disease models and their modulation with HDAC inhibitors are also discussed. Significance of these HDAC inhibitors has been reviewed on the process of neuronal differentiation, neurite outgrowth and neuroprotection regarding their potential therapeutic application for treatment of neurodegenerative diseases.
组蛋白去乙酰化酶（HADC）是一种能从组蛋白和非组蛋白的赖氨酸残基上去除乙酰基的酶，它通过与转录因子结合来调节转录过程，并调控细胞增殖、分化和发育等基本细胞过程。在神经退行性疾病中，组蛋白乙酰化稳态受到极大破坏，向低乙酰化状态转变。直接抑制HDACs产生的组蛋白高乙酰化会导致神经保护作用。本综述试图阐述HDACs小分子抑制剂在神经元分化中的作用，并揭示HDAC抑制剂作为治疗神经退行性疾病治疗药物的潜力。还讨论了HDACs在神经元细胞和疾病模型中的作用及其与HDAC抑制剂的调节作用。就HDAC抑制剂在神经元分化、神经突生长和神经保护过程中的潜在治疗应用而言，其意义已得到综述，这些应用涉及它们对神经退行性疾病的治疗。
