组蛋白去乙酰化酶抑制剂作为神经疾病治疗药物的研发
Development of histone deacetylase inhibitors as therapeutics for neurological disease.
作者信息
Gottesfeld Joel M, Pandolfo Massimo
机构信息
Department of Molecular Biology, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA, Tel.: +1 858 784 8913.
出版信息
Future Neurol. 2009 Nov 1;4(6):775-784. doi: 10.2217/fnl.09.55.
Abstract
Postsynthetic modifications of histone and other chromosomal proteins by reversible acetylation and/or methylation regulate many aspects of chromatin dynamics, such as transcription, replication and DNA repair. Aberrant modification states are associated with several neurological and neuromotor diseases. Thus, small molecules that inhibit or activate the enzymes responsible for these chromatin modifications have received considerable attention as potential human therapeutics. This paper summarizes the current state of development of histone deacetylase inhibitors in a variety of neurological diseases.
摘要
组蛋白和其他染色体蛋白通过可逆的乙酰化和/或甲基化进行的合成后修饰调节染色质动力学的许多方面，如转录、复制和DNA修复。异常的修饰状态与多种神经和神经运动疾病相关。因此，抑制或激活负责这些染色质修饰的酶的小分子作为潜在的人类治疗药物受到了广泛关注。本文总结了组蛋白脱乙酰酶抑制剂在多种神经疾病中的当前发展状况。
相似文献
1
Development of histone deacetylase inhibitors as therapeutics for neurological disease.组蛋白去乙酰化酶抑制剂作为神经疾病治疗药物的研发
Future Neurol. 2009 Nov 1;4(6):775-784. doi: 10.2217/fnl.09.55.
2
Small molecule modulators of histone acetylation and methylation: a disease perspective.组蛋白乙酰化和甲基化的小分子调节剂：疾病视角
Biochim Biophys Acta. 2010 Oct-Dec;1799(10-12):810-28. doi: 10.1016/j.bbagrm.2010.09.005. Epub 2010 Oct 1.
3
Precipitous release of methyl-CpG binding protein 2 and histone deacetylase 1 from the methylated human multidrug resistance gene (MDR1) on activation.激活时甲基化的人类多药耐药基因（MDR1）上甲基-CpG结合蛋白2和组蛋白去乙酰化酶1的快速释放
Mol Cell Biol. 2002 Mar;22(6):1844-57. doi: 10.1128/MCB.22.6.1844-1857.2002.
4
Mammalian DNA repair: HATs and HDACs make their mark through histone acetylation.哺乳动物 DNA 修复：通过组蛋白乙酰化，HATs 和 HDACs 留下了自己的印记。
Mutat Res. 2013 Oct;750(1-2):23-30. doi: 10.1016/j.mrfmmm.2013.07.002. Epub 2013 Aug 6.
5
Histone acetyl transferases: a role in DNA repair and DNA replication.组蛋白乙酰转移酶：在DNA修复和DNA复制中的作用。
J Mol Med (Berl). 2002 Aug;80(8):463-74. doi: 10.1007/s00109-002-0341-7. Epub 2002 May 22.
6
Histone acetylation dynamics in repair of DNA double-strand breaks.DNA双链断裂修复中的组蛋白乙酰化动力学
Front Genet. 2022 Sep 9;13:926577. doi: 10.3389/fgene.2022.926577. eCollection 2022.
7
[DNA methyltransferase inhibitors * histone deacetylase inhibitors].[DNA甲基转移酶抑制剂 * 组蛋白去乙酰化酶抑制剂]
Nihon Rinsho. 2014 Jun;72(6):1136-42.
8
Epigenetic regulation of memory by acetylation and methylation of chromatin: implications in neurological disorders, aging, and addiction.染色质乙酰化和甲基化对记忆的表观遗传调控：对神经疾病、衰老和成瘾的影响
Neuromolecular Med. 2015 Jun;17(2):97-110. doi: 10.1007/s12017-014-8306-x. Epub 2014 Apr 29.
9
Chromatin dynamics: interplay between remodeling enzymes and histone modifications.染色质动力学：重塑酶与组蛋白修饰之间的相互作用
Biochim Biophys Acta. 2014 Aug;1839(8):728-36. doi: 10.1016/j.bbagrm.2014.02.013. Epub 2014 Feb 28.
10
Advances in Epigenetic Cancer Therapeutics.表观遗传学癌症治疗的进展
Cureus. 2020 Nov 27;12(11):e11725. doi: 10.7759/cureus.11725.
引用本文的文献
1
Suberoylanilide Hydroxamic Acid (SAHA) Is a Driver Molecule of Neuroplasticity: Implication for Neurological Diseases.辛二酰苯胺异羟肟酸（SAHA）是神经可塑性的驱动分子：对神经系统疾病的启示。
Biomolecules. 2023 Aug 24;13(9):1301. doi: 10.3390/biom13091301.
2
Clinical improvement of DM1 patients reflected by reversal of disease-induced gene expression in blood.1 型糖尿病患者的临床改善反映在血液中疾病诱导的基因表达逆转。
BMC Med. 2022 Nov 10;20(1):395. doi: 10.1186/s12916-022-02591-y.
3
IOX1 impedes host inflammation in imiquimod-triggered psoriasis.IOX1可抑制咪喹莫特诱发的银屑病中的宿主炎症反应。
Heliyon. 2021 Nov 19;7(11):e08433. doi: 10.1016/j.heliyon.2021.e08433. eCollection 2021 Nov.
4
New developments in Huntington's disease and other triplet repeat diseases: DNA repair turns to the dark side.亨廷顿舞蹈症及其他三联体重复序列疾病的新进展：DNA修复走向黑暗面。
Neuronal Signal. 2020 Nov 16;4(4):NS20200010. doi: 10.1042/NS20200010. eCollection 2020 Dec.
5
Epigenetic Reexpression of Hemoglobin F Using Reversible LSD1 Inhibitors: Potential Therapies for Sickle Cell Disease.使用可逆性赖氨酸特异性去甲基化酶1（LSD1）抑制剂实现血红蛋白F的表观遗传重表达：镰状细胞病的潜在治疗方法
ACS Omega. 2020 Jun 9;5(24):14750-14758. doi: 10.1021/acsomega.0c01585. eCollection 2020 Jun 23.
6
Inhibition of the histone demethylase KDM4B leads to activation of KDM1A, attenuates bacterial-induced pro-inflammatory cytokine release, and reduces osteoclastogenesis.组蛋白去甲基化酶 KDM4B 的抑制导致 KDM1A 的激活，减弱了细菌诱导的促炎细胞因子释放，并减少了破骨细胞的生成。
Epigenetics. 2018;13(5):557-572. doi: 10.1080/15592294.2018.1481703. Epub 2018 Aug 7.
7
A flow cytometry-based screen identifies MBNL1 modulators that rescue splicing defects in myotonic dystrophy type I.基于流式细胞术的筛选鉴定出可挽救I型强直性肌营养不良症剪接缺陷的MBNL1调节剂。
Hum Mol Genet. 2017 Aug 15;26(16):3056-3068. doi: 10.1093/hmg/ddx190.
8
3,5-Diamino-1,2,4-triazoles as a novel scaffold for potent, reversible LSD1 (KDM1A) inhibitors.3,5-二氨基-1,2,4-三唑作为一种新型骨架用于高效、可逆的赖氨酸特异性去甲基化酶1（KDM1A）抑制剂。
Medchemcomm. 2014 Dec;5(12):1863-1870. doi: 10.1039/C4MD00283K.
9
Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich ataxia.弗里德赖希共济失调YAC转基因小鼠模型的细胞、分子及功能特性研究
PLoS One. 2014 Sep 8;9(9):e107416. doi: 10.1371/journal.pone.0107416. eCollection 2014.
10
Role of histone deacetylase activity in the developing lateral line neuromast of zebrafish larvae.组蛋白去乙酰化酶活性在斑马鱼幼虫侧线neuro 嵴发育中的作用。
Exp Mol Med. 2014 May 9;46(5):e94. doi: 10.1038/emm.2014.18.
本文引用的文献
1
LBH589 induces up to 10-fold SMN protein levels by several independent mechanisms and is effective even in cells from SMA patients non-responsive to valproate.LBH589通过多种独立机制使生存运动神经元（SMN）蛋白水平提高多达10倍，甚至在对丙戊酸无反应的脊髓性肌萎缩症（SMA）患者的细胞中也有效。
Hum Mol Genet. 2009 Oct 1;18(19):3645-58. doi: 10.1093/hmg/ddp313. Epub 2009 Jul 7.
2
Stereoselective HDAC inhibition from cysteine-derived zinc-binding groups.源自半胱氨酸的锌结合基团的立体选择性组蛋白去乙酰化酶抑制作用。
ChemMedChem. 2009 Aug;4(8):1292-301. doi: 10.1002/cmdc.200900088.
3
Phase II open label study of valproic acid in spinal muscular atrophy.丙戊酸治疗脊髓性肌萎缩的II期开放标签研究。
PLoS One. 2009;4(5):e5268. doi: 10.1371/journal.pone.0005268. Epub 2009 May 14.
4
Studies of benzamide- and thiol-based histone deacetylase inhibitors in models of oxidative-stress-induced neuronal death: identification of some HDAC3-selective inhibitors.基于苯甲酰胺和硫醇的组蛋白去乙酰化酶抑制剂在氧化应激诱导的神经元死亡模型中的研究：一些HDAC3选择性抑制剂的鉴定。
ChemMedChem. 2009 May;4(5):842-52. doi: 10.1002/cmdc.200800461.
5
MeCP2-mediated transcription repression in the basolateral amygdala may underlie heightened anxiety in a mouse model of Rett syndrome.在基底外侧杏仁核中，MeCP2介导的转录抑制可能是雷特综合征小鼠模型中焦虑加剧的潜在原因。
J Neurosci. 2009 Apr 1;29(13):4218-27. doi: 10.1523/JNEUROSCI.4225-08.2009.
6
Recent advances in MeCP2 structure and function.甲基化CpG结合蛋白2（MeCP2）结构与功能的最新进展。
Biochem Cell Biol. 2009 Feb;87(1):219-27. doi: 10.1139/O08-115.
7
Mechanism of p300 specific histone acetyltransferase inhibition by small molecules.小分子对p300特异性组蛋白乙酰转移酶的抑制机制。
J Med Chem. 2009 Jan 22;52(2):267-77. doi: 10.1021/jm800657z.
8
Catalysis and substrate selection by histone/protein lysine acetyltransferases.组蛋白/蛋白质赖氨酸乙酰转移酶的催化作用与底物选择
Curr Opin Struct Biol. 2008 Dec;18(6):682-9. doi: 10.1016/j.sbi.2008.11.004.
9
Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition.通过DNA甲基化导致的生存运动神经元基因2沉默与脊髓性肌萎缩症的疾病严重程度相关，并且可以通过组蛋白脱乙酰酶抑制作用来规避。
Hum Mol Genet. 2009 Jan 15;18(2):304-17. doi: 10.1093/hmg/ddn357. Epub 2008 Oct 29.
10
Pimelic diphenylamide 106 is a slow, tight-binding inhibitor of class I histone deacetylases.庚二酸二苯酰胺106是一种I类组蛋白去乙酰化酶的缓慢、紧密结合抑制剂。
J Biol Chem. 2008 Dec 19;283(51):35402-9. doi: 10.1074/jbc.M807045200. Epub 2008 Oct 24.
Zotero 插件