Lagali Pamela S, Picketts David J
Regenerative Medicine Program, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON Canada K1H 8L6 ; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON Canada K1H 8M5.
J Ocul Biol Dis Infor. 2011 Sep;4(3):111-20. doi: 10.1007/s12177-012-9080-3. Epub 2012 Mar 17.
Retinal neurons are highly vulnerable to a diverse array of neurotoxic stimuli that leads to their degeneration, which is a major contributor to blindness. This review summarizes the role of epigenetic factors in mediating neuronal homeostasis and survival to protect against cell death and neurodegenerative conditions. Studies in human patients and mouse models implicate numerous chromatin modifications in neuroprotective processes including histone protein acetylation and methylation, DNA methylation, and ATP-dependent nucleosome remodeling. Recent research has begun to uncover specific epigenetic mechanisms invoked by neurotoxic stimuli. Continued investigation in this area will be the key to the generation of therapeutic strategies for the intervention of retinal neurodegenerative diseases.
视网膜神经元极易受到多种神经毒性刺激的影响,这些刺激会导致其退化,而这是导致失明的主要原因。本综述总结了表观遗传因素在介导神经元稳态和存活以防止细胞死亡和神经退行性疾病方面的作用。对人类患者和小鼠模型的研究表明,包括组蛋白乙酰化和甲基化、DNA甲基化以及ATP依赖的核小体重塑在内的多种染色质修饰参与了神经保护过程。最近的研究已开始揭示神经毒性刺激所引发的特定表观遗传机制。该领域的持续研究将是生成干预视网膜神经退行性疾病治疗策略的关键。