摘要
肌萎缩侧索硬化症(ALS)是以运动神经元退化和胶质激活为特征的成人型运动神经元疾病,最终导致运动性肌损和瘫痪。对许多不同的治疗性干预进行了检查,但是目前并没有治疗ALS紊乱的治愈方法或有效的治疗方法。谷氨酸介导的兴奋性毒性、炎症、线粒体功能障碍、氧化应激、蛋白聚集、转录下调,及表现遗传修饰是ALS发病的相关机制,并作为已知的ALS治疗靶点。在本综述中,为了改善ALS,我们讨论了以表现遗传学组分为靶点的平移药理学。对表观遗传机制的研究会给我们提供新的视角,将使我们进一步识别治疗ALS 的潜在生物标记物和治疗方法。治疗ALS最有效的方法就是表现遗传学组分修饰和多靶点的联合治疗。
关键词: 肌萎缩侧索硬化症,表现遗传学组分,HDAC抑制剂,运动神经元,转录,疗法
Current Medicinal Chemistry
Title:Therapeutic Targeting of Epigenetic Components in Amyotrophic Lateral Sclerosis (ALS)
Volume: 21 Issue: 31
Author(s): J. Lee, H. Ryu, G. Keum, Y.J. Yoon, N.W. Kowall and H. Ryu
Affiliation:
关键词: 肌萎缩侧索硬化症,表现遗传学组分,HDAC抑制剂,运动神经元,转录,疗法
摘要: 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.
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Cite this article as:
Lee J., Ryu H., Keum G., Yoon Y.J., Kowall N.W. and Ryu H., Therapeutic Targeting of Epigenetic Components in Amyotrophic Lateral Sclerosis (ALS), Current Medicinal Chemistry 2014; 21 (31) . https://dx.doi.org/10.2174/0929867321666140706131825
DOI https://dx.doi.org/10.2174/0929867321666140706131825 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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