Aberrant RNA homeostasis in amyotrophic lateral sclerosis: potential for new therapeutic targets?
Aberrant RNA homeostasis in amyotrophic lateral sclerosis: potential for new therapeutic targets?
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DOI：
10.2217/nmt.14.36
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发表时间：
2014
影响因子：
2.6
通讯作者：
Sattler R
中科院分区：
文献类型：
--
作者：
Donnelly CJ;Grima JC;Sattler R
肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是一种以进行性运动神经元变性为特征的致死性神经退行性疾病。疾病的发病机制是多方面的，因为已经确定多种细胞和分子途径是疾病进展的贡献者。因此，许多治疗靶点已被用于临床开发，不幸的是几乎没有成功。最近发现的RNA调节基因（如TARDBP/TDP-43、FUS/TLS或C9 ORF 72）突变改变了我们对ALS神经退行性机制的理解，并引入了功能失调的RNA加工作为疾病发病机制的重要贡献者。本文讨论了ALS中这种RNA毒性途径的最新发现和潜在的新治疗方法。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration. The disease pathogenesis is multifaceted in that multiple cellular and molecular pathways have been identified as contributors to the disease progression. Consequently, numerous therapeutic targets have been pursued for clinical development, unfortunately with little success. The recent discovery of mutations in RNA modulating genes such as TARDBP/TDP-43, FUS/TLS or C9ORF72 changed our understanding of neurodegenerative mechanisms in ALS and introduced the role of dysfunctional RNA processing as a significant contributor to disease pathogenesis. This article discusses the latest findings on such RNA toxicity pathways in ALS and potential novel therapeutic approaches.