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Inhibition of BET bromodomain targets genetically diverse glioblastoma.抑制 BET 溴结构域靶点可治疗遗传异质性脑胶质瘤。
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开发用于脑部疾病的表观遗传学诊断和治疗方法。

Developing epigenetic diagnostics and therapeutics for brain disorders.

机构信息

Roslyn and Leslie Goldstein Laboratory for Stem Cell Biology and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Institute for Brain Disorders and Neural Regeneration, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Rose F. Kennedy Center for Research on Intellectual and Developmental Disabilities, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

出版信息

Trends Mol Med. 2013 Dec;19(12):732-41. doi: 10.1016/j.molmed.2013.09.003. Epub 2013 Oct 18.

DOI:10.1016/j.molmed.2013.09.003
PMID:24145019
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3855296/
Abstract

Perturbations in epigenetic mechanisms have emerged as cardinal features in the molecular pathology of major classes of brain disorders. We therefore highlight evidence which suggests that specific epigenetic signatures measurable in central - and possibly even in peripheral tissues - have significant value as translatable biomarkers for screening, early diagnosis, and prognostication; developing molecularly targeted medicines; and monitoring disease progression and treatment responses. We also draw attention to existing and novel therapeutic approaches directed at epigenetic factors and mechanisms, including strategies for modulating enzymes that write and erase DNA methylation and histone/chromatin marks; protein-protein interactions responsible for reading epigenetic marks; and non-coding RNA pathways.

摘要

表观遗传机制的紊乱已成为主要脑部疾病的分子病理学的主要特征。因此,我们强调了一些证据,表明中枢神经系统(甚至可能在外周组织)中可测量的特定表观遗传特征具有重要价值,可作为用于筛选、早期诊断和预后的可转化生物标志物;开发针对特定分子靶点的药物;以及监测疾病进展和治疗反应。我们还提请注意针对表观遗传因素和机制的现有和新的治疗方法,包括调节写入和擦除 DNA 甲基化和组蛋白/染色质标记的酶的策略;负责读取表观遗传标记的蛋白质-蛋白质相互作用;以及非编码 RNA 途径。