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神经系统的新型治疗策略:生物钟基因、非编码RNA和叉头转录因子

Novel Treatment Strategies for the Nervous System: Circadian Clock Genes, Non-coding RNAs, and Forkhead Transcription Factors.

作者信息

Maiese Kenneth

机构信息

New Jersey Cellular Sciences University, Newark, New Jersey 07101, United States.

出版信息

Curr Neurovasc Res. 2018;15(1):81-91. doi: 10.2174/1567202615666180319151244.

DOI:10.2174/1567202615666180319151244
PMID:29557749
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6021214/
Abstract

BACKGROUND

With the global increase in lifespan expectancy, neurodegenerative disorders continue to affect an ever-increasing number of individuals throughout the world. New treatment strategies for neurodegenerative diseases are desperately required given the lack of current treatment modalities.

METHODS

Here, we examine novel strategies for neurodegenerative disorders that include circadian clock genes, non-coding Ribonucleic Acids (RNAs), and the mammalian forkhead transcription factors of the O class (FoxOs).

RESULTS

Circadian clock genes, non-coding RNAs, and FoxOs offer exciting prospects to potentially limit or remove the significant disability and death associated with neurodegenerative disorders. Each of these pathways has an intimate relationship with the programmed death pathways of autophagy and apoptosis and share a common link to the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) and the mechanistic target of rapamycin (mTOR). Circadian clock genes are necessary to modulate autophagy, limit cognitive loss, and prevent neuronal injury. Non-coding RNAs can control neuronal stem cell development and neuronal differentiation and offer protection against vascular disease such as atherosclerosis. FoxOs provide exciting prospects to block neuronal apoptotic death and to activate pathways of autophagy to remove toxic accumulations in neurons that can lead to neurodegenerative disorders.

CONCLUSION

Continued work with circadian clock genes, non-coding RNAs, and FoxOs can offer new prospects and hope for the development of vital strategies for the treatment of neurodegenerative diseases. These innovative investigative avenues have the potential to significantly limit disability and death from these devastating disorders.

摘要

背景

随着全球预期寿命的增加,神经退行性疾病在全球范围内持续影响着越来越多的人。鉴于目前缺乏有效的治疗方式,迫切需要针对神经退行性疾病的新治疗策略。

方法

在此,我们研究了针对神经退行性疾病的新策略,包括生物钟基因、非编码核糖核酸(RNA)和O类哺乳动物叉头转录因子(FoxOs)。

结果

生物钟基因、非编码RNA和FoxOs为潜在地限制或消除与神经退行性疾病相关的严重残疾和死亡提供了令人兴奋的前景。这些途径中的每一条都与自噬和凋亡的程序性死亡途径有着密切的关系,并且与沉默交配型信息调节2同源物1(酿酒酵母)(SIRT1)和雷帕霉素靶蛋白(mTOR)有着共同的联系。生物钟基因对于调节自噬、限制认知丧失和预防神经元损伤是必要的。非编码RNA可以控制神经元干细胞的发育和神经元分化,并提供针对诸如动脉粥样硬化等血管疾病的保护。FoxOs为阻断神经元凋亡性死亡和激活自噬途径以清除神经元中可能导致神经退行性疾病的有毒积累物提供了令人兴奋的前景。

结论

对生物钟基因、非编码RNA和FoxOs的持续研究可为神经退行性疾病治疗关键策略的开发提供新的前景和希望。这些创新的研究途径有可能显著限制这些毁灭性疾病导致的残疾和死亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f366/6021214/9a66f9d34310/nihms954526f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f366/6021214/9a66f9d34310/nihms954526f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f366/6021214/9a66f9d34310/nihms954526f1.jpg

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