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表观遗传学修饰作为亨廷顿病的新治疗靶点。

Epigenetic modifications as novel therapeutic targets for Huntington's disease.

机构信息

State Key Laboratory of Biomembrane & Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Epigenomics. 2014 Jun;6(3):287-97. doi: 10.2217/epi.14.19.


DOI:10.2217/epi.14.19
PMID:25111483
Abstract

Huntington's disease is a late-onset, autosomal dominant neurodegenerative disorder characterized by motor, cognitive and psychiatric symptomatology. The earliest stage of Huntington's disease is marked by alterations in gene expression, which partially results from dysregulated epigenetic modifications. In past decades, altered epigenetic markers including histone modifications (acetylation, methylation, ubiquitylation and phosphorylation) and DNA modifications (cytosine methylation and hydroxymethylation) have been reported as important epigenetic features in patients and multiple animal models of Huntington's disease. Drugs aimed to correct some of those alterations have shown promise in treating Huntington's disease. This article discusses the field of epigenetics for potential Huntington's disease interventions and presents the most recent findings in this area.

摘要

亨廷顿病是一种迟发性、常染色体显性神经退行性疾病,其特征为运动、认知和精神症状。亨廷顿病的最早阶段表现为基因表达的改变,这部分是由于表观遗传修饰的失调所致。在过去的几十年中,改变的表观遗传标记物,包括组蛋白修饰(乙酰化、甲基化、泛素化和磷酸化)和 DNA 修饰(胞嘧啶甲基化和羟甲基化),已被报道为亨廷顿病患者和多种动物模型中的重要表观遗传特征。旨在纠正其中一些改变的药物在治疗亨廷顿病方面显示出了希望。本文讨论了针对亨廷顿病干预的表观遗传学领域,并介绍了该领域的最新发现。

相似文献

[1]
Epigenetic modifications as novel therapeutic targets for Huntington's disease.

Epigenomics. 2014-6

[2]
Epigenetic Mechanisms Involved in Huntington's Disease Pathogenesis.

J Huntingtons Dis. 2015

[3]
Epigenetics of Huntington's Disease.

Adv Exp Med Biol. 2017

[4]
Epigenetic-based therapies in the preclinical and clinical treatment of Huntington's disease.

Int J Biochem Cell Biol. 2015-10

[5]
What's wrong with epigenetics in Huntington's disease?

Neuropharmacology. 2014-5

[6]
HDAC inhibition imparts beneficial transgenerational effects in Huntington's disease mice via altered DNA and histone methylation.

Proc Natl Acad Sci U S A. 2015-1-6

[7]
Modulation of nucleosome dynamics in Huntington's disease.

Hum Mol Genet. 2007-5-15

[8]
Histone deacetylase inhibitors: a novel therapeutic approach to Huntington's disease (complex mechanism of neuronal death).

Curr Alzheimer Res. 2006-9

[9]
Mechanisms of disease: Histone modifications in Huntington's disease.

Nat Clin Pract Neurol. 2006-6

[10]
Histone post-translational modifications in Huntington's and Parkinson's diseases.

Curr Pharm Des. 2013

引用本文的文献

[1]
G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.

Med Res Rev. 2025-5

[2]
Unlocking the epigenetic symphony: histone acetylation's impact on neurobehavioral change in neurodegenerative disorders.

Epigenomics. 2024-3

[3]
Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration.

Cell Biosci. 2023-1-16

[4]
The Essential Role of Epigenetic Modifications in Neurodegenerative Diseases with Dyskinesia.

Cell Mol Neurobiol. 2022-11

[5]
Histone Methylation Regulation in Neurodegenerative Disorders.

Int J Mol Sci. 2021-4-28

[6]
Epigenetic Changes and Its Intervention in Age-Related Neurodegenerative Diseases.

Cell Mol Neurobiol. 2022-4

[7]
Contribution of Neuroepigenetics to Huntington's Disease.

Front Hum Neurosci. 2017-1-30

[8]
Multiregional analysis of global 5-methylcytosine and 5-hydroxymethylcytosine throughout the progression of Alzheimer's disease.

J Neurochem. 2017-2

[9]
Inhibition of DNA Methyltransferases Blocks Mutant Huntingtin-Induced Neurotoxicity.

Sci Rep. 2016-8-12

[10]
Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

Aging (Albany NY). 2016-7

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