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微小RNA在血管性认知障碍中血脑屏障功能障碍中的作用

Role of microRNAs on Blood Brain Barrier Dysfunction in Vascular Cognitive Impairment.

作者信息

Toyama Kensuke, Spin Joshua Michael, Tsao Philip Shih

机构信息

Department of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.

VA Palo Alto Health Care System, Palo Alto, California, USA.

出版信息

Curr Drug Deliv. 2017 Sep 6;14(6):744-757. doi: 10.2174/1567201813666160830124627.

Abstract

BACKGROUND

Dementia cases are increasing as the population ages, leading to increased financial costs. Several neuronal diseases including ischemic and hemorrhagic stroke involve cerebrovascular injury or pathophysiology. Cerebrovascular injury is closely tied to blood brain barrier (BBB) disruption. Many studies have shown a significant association between BBB dysfunction and neurological diseases. Therefore, an understanding of the molecular mechanisms which regulate BBB permeability and disruption is essential for establishing future therapeutic strategies to alter dementia disease progression related to cerebrovascular injury, so-called vascular cognitive impairment (VCI). microRNAs (miRs) are small non-coding RNAs that regulate gene expression through targeting of mRNA transcripts. miRs have been implicated in the development and progression of various illnesses, including vascular disease. However, the role of miRs in BBB breakdown or permeability and VCI development has not yet been well clarified.

METHOD

Research content related to the origins of VCI and the role of the BBB in pathologic development and therapeutic targeting are reviewed, including current relevant animal models. We draw from the published literature regarding microRNA candidates that are associated with modulation of BBB structure and function.

RESULTS

In this review, we summarize the current knowledge about VCI, explore the potential role of miRs in BBB breakdown and VCI progression, and identify potential candidate miRs for development of new treatment strategies.

CONCLUSION

miRs constitute a promising novel avenue as future therapeutic options for alteration of both BBB permeability and development of VCI.

摘要

背景

随着人口老龄化,痴呆病例不断增加,导致经济成本上升。包括缺血性和出血性中风在内的几种神经疾病涉及脑血管损伤或病理生理学。脑血管损伤与血脑屏障(BBB)破坏密切相关。许多研究表明血脑屏障功能障碍与神经疾病之间存在显著关联。因此,了解调节血脑屏障通透性和破坏的分子机制对于制定未来治疗策略以改变与脑血管损伤相关的痴呆疾病进展(即所谓的血管性认知障碍,VCI)至关重要。微小RNA(miRs)是一类小的非编码RNA,通过靶向mRNA转录本来调节基因表达。miRs已被证明与包括血管疾病在内的各种疾病的发生和发展有关。然而,miRs在血脑屏障破坏或通透性以及VCI发展中的作用尚未得到充分阐明。

方法

综述了与VCI起源以及血脑屏障在病理发展和治疗靶点中的作用相关的研究内容,包括当前相关的动物模型。我们参考了已发表的关于与血脑屏障结构和功能调节相关的微小RNA候选物的文献。

结果

在本综述中,我们总结了关于VCI的现有知识,探讨了miRs在血脑屏障破坏和VCI进展中的潜在作用,并确定了用于开发新治疗策略的潜在候选miRs。

结论

miRs作为未来改变血脑屏障通透性和VCI发展的治疗选择,构成了一条有前景的新途径。

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