Department of Neurology, University of Michigan, 1500 East Medical Centre Drive, 1914 Taubman Centre SPC 5316, Ann Arbor, MI 48109, USA.
The A. Alfred Taubman Medical Research Institute, University of Michigan, 109 Zina Pitcher Place, 5017 A. Alfred Taubman Biomedical Science Research Building, Ann Arbor, MI 48109, USA.
Nat Rev Neurol. 2015 May;11(5):266-79. doi: 10.1038/nrneurol.2015.57. Epub 2015 Apr 21.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of the motor neurons, which results in weakness and atrophy of voluntary skeletal muscles. Treatments do not modify the disease trajectory effectively, and only modestly improve survival. A complex interaction between genes, environmental exposure and impaired molecular pathways contributes to pathology in patients with ALS. Epigenetic mechanisms control the hereditary and reversible regulation of gene expression without altering the basic genetic code. Aberrant epigenetic patterns-including abnormal microRNA (miRNA) biogenesis and function, DNA modifications, histone remodeling, and RNA editing-are acquired throughout life and are influenced by environmental factors. Thus, understanding the molecular processes that lead to epigenetic dysregulation in patients with ALS might facilitate the discovery of novel therapeutic targets and biomarkers that could reduce diagnostic delay. These achievements could prove crucial for successful disease modification in patients with ALS. We review the latest findings regarding the role of miRNA modifications and other epigenetic mechanisms in ALS, and discuss their potential as therapeutic targets.
肌萎缩侧索硬化症（ALS）是一种运动神经元的进行性神经退行性疾病，导致随意骨骼肌的无力和萎缩。治疗方法并不能有效地改变疾病进程，只能适度地延长生存时间。基因、环境暴露和受损的分子途径之间的复杂相互作用导致 ALS 患者的病理变化。表观遗传机制控制基因表达的遗传和可逆调节，而不会改变基本的遗传密码。异常的表观遗传模式——包括异常的 microRNA（miRNA）生物发生和功能、DNA 修饰、组蛋白重塑和 RNA 编辑——在整个生命周期中获得，并受环境因素影响。因此，了解导致 ALS 患者表观遗传失调的分子过程可能有助于发现新的治疗靶点和生物标志物，从而减少诊断延迟。这些成就在 ALS 患者的成功疾病修饰中可能被证明是至关重要的。我们综述了 miRNA 修饰和其他表观遗传机制在 ALS 中的作用的最新发现，并讨论了它们作为治疗靶点的潜力。
