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组蛋白翻译后修饰在神经退行性疾病中的作用。

The impact of histone post-translational modifications in neurodegenerative diseases.

机构信息

Chemistry Department of Brooklyn College, Brooklyn, New York 11210, United States; Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY 10016, United States.

Chemistry Department of Brooklyn College, Brooklyn, New York 11210, United States; Ph.D. Program in Biochemistry, The Graduate Center of the City University of New York, New York, NY 10016, United States.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2019 Aug 1;1865(8):1982-1991. doi: 10.1016/j.bbadis.2018.10.019. Epub 2018 Oct 20.

Abstract

Every year, neurodegenerative disorders take more than 5000 lives in the US alone. Cures have not yet been found for many of the multitude of neuropathies. The majority of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Parkinson's disease (PD) cases have no known genetic basis. Thus, it is evident that contemporary genetic approaches have failed to explain the etiology or etiologies of ALS/FTD and PD. Recent investigations have explored the potential role of epigenetic mechanisms in disease development. Epigenetics comprises heritable changes in gene utilization that are not derived from changes in the genome. A main epigenetic mechanism involves the post-translational modification of histones. Increased knowledge of the epigenomic landscape of neurodegenerative diseases would not only further our understanding of the disease pathologies, but also lead to the development of treatments able to halt their progress. Here, we review recent advances on the association of histone post-translational modifications with ALS, FTD, PD and several ataxias.

摘要

每年,仅在美国,神经退行性疾病就夺走了 5000 多人的生命。对于许多神经病变,还没有找到治愈方法。大多数肌萎缩侧索硬化症(ALS)、额颞叶痴呆(FTD)和帕金森病(PD)病例没有已知的遗传基础。因此,很明显,当代遗传方法未能解释 ALS/FTD 和 PD 的病因。最近的研究探讨了表观遗传机制在疾病发展中的潜在作用。表观遗传学包括基因利用的可遗传变化,这些变化不是源自基因组的变化。一个主要的表观遗传机制涉及组蛋白的翻译后修饰。增加对神经退行性疾病表观基因组景观的了解,不仅将加深我们对疾病病理学的理解,还将导致开发能够阻止其进展的治疗方法。在这里,我们回顾了组蛋白翻译后修饰与 ALS、FTD、PD 和几种共济失调相关的最新进展。

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