Epigenetics in amyotrophic lateral sclerosis: a role for histone post-translational modifications in neurodegenerative disease.

Epigenetics in amyotrophic lateral sclerosis: a role for histone post-translational modifications in neurodegenerative disease.
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DOI:
10.1016/j.trsl.2018.10.002
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发表时间:
2019-03
期刊:
Translational research : the journal of laboratory and clinical medicine
影响因子:
--
通讯作者:
Torrente MP
Torrente MP
中科院分区:
其他
文献类型:
--
作者:
Bennett SA;Tanaz R;Cobos SN;Torrente MP

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肌萎缩侧索硬化症 (ALS) 是全球第三大最常见的成人发病神经退行性疾病。它的一般特征是从四肢开始进行性瘫痪,最终导致呼吸衰竭而死亡。目前尚无治愈方法,目前的治疗方法也无法减缓疾病的进展。因此,迫切需要新的治疗方案。表观遗传目标是一种有吸引力的可能性,因为它们是可逆的。表观遗传学是指与 DNA 序列变化无关的基因表达的遗传变化。三种主要的表观遗传机制包括 DNA 甲基化、微小 RNA 和组蛋白翻译后修饰。组蛋白修饰发生在许多氨基酸残基中,包括磷酸化、乙酰化、甲基化以及其他化学部分。最近的证据表明表观遗传机制在 ALS 病因学中可能发挥作用。在这里,我们回顾了 ALS 和表观遗传学之间的最新进展,重点关注组蛋白修饰。组蛋白修饰谱的局部和整体变化都与 ALS 相关,引起人们对未来诊断和治疗方法的潜在目标的关注。
Amyotrophic Lateral Sclerosis (ALS) is the third most common adult onset neurodegenerative disorder worldwide. It is generally characterized by progressive paralysis starting at the limbs ultimately leading to death caused by respiratory failure. There is no cure and current treatments fail to slow the progression of the disease. As such, new treatment options are desperately needed. Epigenetic targets are an attractive possibility because they are reversible. Epigenetics refers to heritable changes in gene expression unrelated to changes in DNA sequence. Three main epigenetic mechanisms include the methylation of DNA, micro-RNAs and the post-translational modification of histone proteins. Histone modifications occur in many amino acid residues and include phosphorylation, acetylation, methylation as well as other chemical moieties. Recent evidence points to a possible role for epigenetic mechanisms in the etiology of ALS. Here we review recent advances linking ALS and epigenetics, with a strong focus on histone modifications. Both local and global changes in histone modification profiles are associated with ALS drawing attention to potential targets for future diagnostic and treatment approaches.
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