Department of Neurology, Pittsburgh Institute of Brain Disorders & Recovery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
CNS Neurosci Ther. 2020 Dec;26(12):1207-1218. doi: 10.1111/cns.13472.
Vascular cognitive impairment and dementia (VCID) is defined as a progressive dementia disease related to cerebrovascular injury and often occurs in aged populations. Despite decades of research, effective treatment for VCID is still absent. The pathological processes of VCID are mediated by the molecular mechanisms that are partly modulated at the post-transcriptional level. As small endogenous non-coding RNAs, microRNAs (miRs) can regulate target gene expression through post-transcriptional gene silencing. miRs have been reported to play an important role in the pathology of VCID and have recently been suggested as potential novel pharmacological targets for the development of new diagnosis and treatment strategies in VCID. In this review, we summarize the current understanding of VCID, the possible role of miRs in the regulation of VCID and attempt to envision future therapeutic strategies. Since manipulation of miR levels by either pharmacological or genetic approaches has shown therapeutic effects in experimental VCID models, we also emphasize the potential therapeutic value of miRs in clinical settings.
血管性认知障碍和痴呆(VCID)定义为一种与脑血管损伤相关的进行性痴呆疾病,常见于老年人群。尽管已经进行了数十年的研究,但仍缺乏有效的 VCID 治疗方法。VCID 的病理过程受分子机制介导,这些机制部分在转录后水平上受到调节。作为小的内源性非编码 RNA,microRNAs(miRs)可以通过转录后基因沉默来调节靶基因的表达。miRs 已被报道在 VCID 的病理中发挥重要作用,并最近被认为是开发 VCID 新诊断和治疗策略的潜在新型药理学靶点。在这篇综述中,我们总结了目前对 VCID 的认识、miRs 在调节 VCID 中的可能作用,并尝试设想未来的治疗策略。由于通过药理学或遗传学方法操纵 miR 水平已在实验性 VCID 模型中显示出治疗效果,因此我们还强调了 miR 在临床环境中的潜在治疗价值。