Lee J, Ryu H, Keum G, Yoon Y J, Kowall N W, Ryu H
VA Boston Healthcare System and Department of Neurology, Boston University School of Medicine, 150 South Huntington Avenue, Boston, MA 02130; USA.
Curr Med Chem. 2014;21(31):3576-82. doi: 10.2174/0929867321666140706131825.
Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease characterized by degeneration of motor neuron and glial activation followed by the progressive muscle loss and paralysis. Numerous distinct therapeutic interventions have been examined but currently ALS does not have a cure or an efficacious treatment for the disorder. Glutamate- induced excitotoxicity, inflammation, mitochondrial dysfunction, oxidative stress, protein aggregation, transcription deregulation, and epigenetic modifications are associated with the pathogenesis of ALS and known to be therapeutic targets in ALS. In this review, we discuss translational pharmacological studies targeting epigenetic components to ameliorate ALS. Understanding of the epigenetic mechanisms will provide novel insights that will further identify potential biological markers and therapeutic approaches for treating ALS. A combination of treatments that modulate epigenetic components and multiple targets may prove to be the most effective therapy for ALS.
肌萎缩侧索硬化症(ALS)是一种成人起病的运动神经元疾病,其特征是运动神经元变性和胶质细胞激活,随后出现进行性肌肉萎缩和瘫痪。已经研究了许多不同的治疗干预措施,但目前ALS尚无治愈方法或有效的治疗手段。谷氨酸诱导的兴奋性毒性、炎症、线粒体功能障碍、氧化应激、蛋白质聚集、转录失调和表观遗传修饰与ALS的发病机制有关,并且已知是ALS的治疗靶点。在本综述中,我们讨论了针对表观遗传成分以改善ALS的转化药理学研究。对表观遗传机制的理解将提供新的见解,这将进一步确定治疗ALS的潜在生物标志物和治疗方法。调节表观遗传成分和多个靶点的联合治疗可能被证明是治疗ALS最有效的疗法。