Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, USA.
J Alzheimers Dis. 2020;75(2):353-383. doi: 10.3233/JAD-200070.
This article reviews recent advances in the study of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and their functions in type 2 diabetes mellitus (T2DM), ischemic stroke (IS), and vascular dementia (VaD). miRNAs and lncRNAs are gene regulation markers that both regulate translational aspects of a wide range of proteins and biological processes in healthy and disease states. Recent studies from our laboratory and others have revealed that miRNAs and lncRNAs expressed differently are potential therapeutic targets for neurological diseases, especially T2DM, IS, VaD, and Alzheimer's disease (AD). Currently, the effect of aging in T2DM, IS, and VaD and the cellular and molecular pathways are largely unknown. In this article, we highlight results from the works on the molecular connections between T2DM and IS, and IS and VaD. In each disease, we also summarize the pathophysiology and the differential expressions of miRNAs and lncRNAs. Based on current research findings, we hypothesize that 1) T2DM bi-directionally and age-dependently induces IS and VaD, and 2) these changes are precursors to the onset of dementia in elderly people. Research into these hypotheses is required to examine further whether research efforts on reducing T2DM, IS, and VaD may affect dementia and/or delay the AD disease process in the aged population.
本文综述了 microRNAs（miRNAs）、长非编码 RNA（lncRNAs）及其在 2 型糖尿病（T2DM）、缺血性中风（IS）和血管性痴呆（VaD）中的功能的最新研究进展。miRNAs 和 lncRNAs 是基因调控标志物，可调节健康和疾病状态下广泛蛋白质和生物过程的翻译方面。本实验室和其他实验室的最近研究表明，表达不同的 miRNAs 和 lncRNAs 是治疗神经疾病（尤其是 T2DM、IS、VaD 和阿尔茨海默病（AD））的潜在治疗靶点。目前，T2DM、IS 和 VaD 的衰老影响以及细胞和分子途径在很大程度上尚不清楚。在本文中，我们重点介绍了关于 T2DM 和 IS 以及 IS 和 VaD 之间分子联系的研究结果。在每种疾病中，我们还总结了 miRNA 和 lncRNA 的病理生理学和差异表达。基于目前的研究结果，我们假设 1）T2DM 双向且与年龄相关地诱导 IS 和 VaD，2）这些变化是老年人痴呆症发病的前兆。需要对这些假设进行研究，以进一步研究减少 T2DM、IS 和 VaD 的研究工作是否会影响痴呆症和/或延缓老年人群中 AD 疾病进程。
