Molecular Insight Into the Therapeutic Potential of Long Non-coding RNA-Associated Competing Endogenous RNA Axes in Alzheimer’s Disease: A Systematic Scoping Review

Abstract

Alzheimer’s disease (AD) is a heterogeneous degenerative brain disorder with a rising prevalence worldwide. The two hallmarks that characterize the AD pathophysiology are amyloid plaques, generated via aggregated amyloid β, and neurofibrillary tangle, generated via accumulated phosphorylated tau. At the post-transcriptional and transcriptional levels, the regulatory functions of non-coding RNAs, in particular long non-coding RNAs (lncRNAs), have been ascertained in gene expressions. It is noteworthy that a number of lncRNAs feature a prevalent role in their potential of regulating gene expression through modulation of microRNAs via a process called the mechanism of competing endogenous RNA (ceRNA). Given the multifactorial nature of ceRNA interaction networks, they might be advantageous in complex disorders (e.g., AD) investigations at the therapeutic targets level. We carried out scoping review in this research to analyze validated loops of ceRNA in AD and focus on ceRNA axes associated with lncRNA. This scoping review was performed according to a six-stage methodology structure and PRISMA guideline. A systematic search of seven databases was conducted to find eligible articles prior to July 2021. Two reviewers independently performed publications screening and data extraction, and quantitative and qualitative analyses were conducted. Fourteen articles were identified that fulfill the inclusion criteria. Studies with different designs reported nine lncRNAs that were experimentally validated to act as ceRNA in AD in human-related studies, including BACE1-AS, SNHG1, RPPH1, NEAT1, LINC00094, SOX21-AS1, LINC00507, MAGI2-AS3, and LINC01311. The BACE1-AS/BACE1 was the most frequent ceRNA pair. Among miRNAs, miR-107 played a key role by regulating three different loops. Understanding the various aspects of this regulatory mechanism can help elucidate the unknown etiology of AD and provide new molecular targets for use in therapeutic and clinical applications.

Identification and Analysis of BCAS4/hsa-miR-185-5p/SHISA7 Competing Endogenous RNA Axis in Late-Onset Alzheimer’s Disease Using Bioinformatic and Experimental Approaches

“…Because of the multifactorial character of ceRNA interacting networks, they may be useful in the research of complicated diseases like AD. As a result, our efforts to comprehend various aspects of ceRNA regulation processes in AD pathology elucidate possible molecular targets, identify biomarkers based on ceRNA, and develop ceRNA-based therapeutic options ( Cai and Wan, 2018 ; Moreno-García et al, 2020 ; Sabaie et al, 2021 ). In this study, we employed bioinformatics and experimental approaches to investigate the BCAS4 / SHISA7 verified ceRNA axis in AD development.…”

Long Non-Coding RNAs, Extracellular Vesicles and Inflammation in Alzheimer’s Disease

“…The dysregulation of ncRNAs associated with AD is well acknowledged [ 38 , 39 ] and lncRNAs in association with AD have been extensively reviewed [ 40 , 41 , 42 , 43 ]. Some studies focus on the role of lncRNAs as potential AD biomarkers [ 44 ], while others focus on lncRNAs showing competing endogenous RNA network (ceRNA) mechanisms [ 45 ]. More recently, a group of lncRNAs has been suggested as potential therapeutic targets for AD [ 46 ].…”

Long Non-coding RNAs, Extracellular Vesicles and Inflammation in Alzheimer’s Disease

“…The dysregulation of ncRNAs associated with AD is well acknowledged [38] [39], and lncRNAs in association with AD have been extensively reviewed [40]- [41]- [43]. Some studies focus on the role of lncRNAs as potential AD biomarkers [44] others focus on lncRNAs showing competing endogenous RNA network (ceRNA) mechanisms [45]. More recently, a group of lncRNAs has been suggested as potential therapeutic targets for AD [46].…”