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利用 SIRT1 和非编码 RNA 在血管疾病中的作用。

Harnessing the Power of SIRT1 and Non-coding RNAs in Vascular Disease.

机构信息

Cellular and Molecular Signaling, Newark, NJ, United States.

出版信息

Curr Neurovasc Res. 2017;14(1):82-88. doi: 10.2174/1567202613666161129112822.

Abstract

Noncommunicable diseases (NCDs) contribute to a significant amount of disability and death in the world. Of these disorders, vascular disease is ranked high, falls within the five leading causes of death, and impacts multiple other disease entities such as those of the cardiac system, nervous system, and metabolic disease. Targeting the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1) pathway and the modulation of micro ribonucleic acids (miRNAs) may hold great promise for the development of novel strategies for the treatment of vascular disease since each of these pathways are highly relevant to cardiac and nervous system disorders as well as to metabolic dysfunction. SIRT1 is vital in determining the course of stem cell development and the survival, metabolism, and life span of differentiated cells that are overseen by both autophagy and apoptosis. SIRT1 interfaces with a number of pathways that involve forkhead transcription factors, mechanistic of rapamycin (mTOR), AMP activated protein kinase (AMPK) and Wnt1 inducible signaling pathway protein 1 (WISP1) such that the level of activity of SIRT1 can become a critical determinant for biological and clinical outcomes. The essential fine control of SIRT1 is directly tied to the world of non-coding RNAs that ultimately oversee SIRT1 activity to either extend or end cellular survival. Future studies that can further elucidate the crosstalk between SIRT1 and non-coding RNAs should serve well our ability to harness the power of SIRT1 and non-coding RNAs for the treatment of vascular disorders.

摘要

非传染性疾病(NCDs)在世界范围内导致了大量的残疾和死亡。在这些疾病中,血管疾病排名很高,属于导致死亡的五个主要原因之一,并影响到多个其他疾病实体,如心血管系统、神经系统和代谢疾病。针对沉默交配型信息调节 2 同源物 1(酿酒酵母)(SIRT1)途径和微小核糖核酸(miRNAs)的调节可能为治疗血管疾病的新策略的发展带来巨大希望,因为这些途径都与心脏和神经系统疾病以及代谢功能障碍密切相关。SIRT1 在决定干细胞发育过程以及自噬和细胞凋亡所监督的分化细胞的存活、代谢和寿命方面至关重要。SIRT1 与许多途径相互作用,包括叉头转录因子、雷帕霉素机制靶蛋白(mTOR)、AMP 激活蛋白激酶(AMPK)和 Wnt1 诱导信号通路蛋白 1(WISP1),因此 SIRT1 的活性水平可以成为生物和临床结果的关键决定因素。SIRT1 的精细控制直接与非编码 RNA 世界相关联,这些非编码 RNA 最终监督 SIRT1 的活性,以延长或终止细胞的存活。未来能够进一步阐明 SIRT1 和非编码 RNA 之间相互作用的研究应该有助于我们利用 SIRT1 和非编码 RNA 的力量来治疗血管疾病。

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