Multiple roles of HDAC inhibition in neurodegenerative conditions.
Multiple roles of HDAC inhibition in neurodegenerative conditions.
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DOI：
10.1016/j.tins.2009.06.002
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发表时间：
2009-11
影响因子：
15.9
通讯作者：
Chiu, Chi-Tso
中科院分区：
文献类型：
--
作者：
Chuang, De-Maw;Leng, Yan;Marinova, Zoya;Kim, Hyeon-Ju;Chiu, Chi-Tso
组蛋白去乙酰化酶（HDAC）在组蛋白和其他蛋白质中的蛋白质乙酰化的稳态中以及在调节基本细胞活动如转录中起关键作用。蛋白质乙酰化水平的不平衡和转录功能障碍与各种各样的脑部疾病有关。用各种HDAC抑制剂治疗纠正了这些缺陷，并且已经成为神经退行性疾病治疗干预的有前途的新策略。在这里，我们回顾并讨论了最近在使用HDAC抑制剂来对抗细胞和疾病模型中的神经退行性疾病方面的有趣进展。HDAC抑制剂具有神经保护、神经营养和抗炎特性，在这些模型中经常看到神经功能、学习/记忆和其他疾病表型的改善。我们讨论了HDAC抑制的这些作用的目标和机制，并评论了一些HDAC抑制剂在治疗神经退行性疾病中证明临床有效的潜力。
Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histones and other proteins and in regulating fundamental cellular activities such as transcription. Imbalances in protein acetylation levels and dysfunctions in transcription are associated with a wide variety of brain disorders. Treatment with various HDAC inhibitors corrects these deficiencies and has emerged as a promising new strategy for therapeutic intervention in neurodegenerative diseases. Here, we review and discuss intriguing recent developments in the use of HDAC inhibitors to combat neurodegenerative conditions in cellular and disease models. HDAC inhibitors have neuroprotective, neurotrophic and anti-inflammatory properties, and improvements in neurological performance, learning/memory and other disease phenotypes are frequently seen in these models. We discuss the targets and mechanisms underlying these effects of HDAC inhibition and comment on the potential for some HDAC inhibitors to prove clinically effective in treating neurodegenerative disorders.
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