The Role of Non-coding RNAs in Alzheimer’s Disease: From Regulated Mechanism to Therapeutic Targets and Diagnostic Biomarkers

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. AD is characterized by the production and aggregation of beta-amyloid (Aβ) peptides, hyperphosphorylated tau proteins that form neurofibrillary tangles (NFTs), and subsequent neuroinflammation, synaptic dysfunction, autophagy and oxidative stress. Non-coding RNAs (ncRNAs) can be used as potential therapeutic targets and biomarkers due to their vital regulatory roles in multiple biological processes involved in disease development. The involvement of ncRNAs in the pathogenesis of AD has been increasingly recognized. Here, we review the ncRNAs implicated in AD and elaborate on their main regulatory pathways, which might have contributions for discovering novel therapeutic targets and drugs for AD.

Posttranscriptional Regulation of Insulin Resistance: Implications for Metabolic Diseases

“…Thus, few studies have explored the potential of targeting miRNAs/RBPS related to IR for the treatment of AD, and further research in this area is needed. Some of the best known miRNAs in the context of IR in AD include miR-200b/c, miR-98, and miR-7, among others [211], and they have in common their impact on components of insulin signaling pathway. For instance, miR-200b/c reduces S6K1 dependent IRS-1pSer and IR and inhibits Aβ production in the human neuroblastoma cell line SH-SY5Y, contributing to positive outcomes in AD [147].…”

LncRNAs as the Regulators of Brain Function and Therapeutic Targets for Alzheimer’s Disease

“…In recent years, with the advancements in sequencing technology, several novel lncRNAs involved in the pathophysiology of AD have been identified, and this knowledge provides novel insights to enhance our understanding of the role of lncRNAs in AD [ 131 , 132 ]. Moreover, some of these lncRNAs have been considered as potential biomarkers and therapeutic targets for AD, although the effect of lncRNAs is complex and relative research on lncRNAs in AD is still limited.…”

Missing lnc(RNAs) in Alzheimer’s Disease?

“…Amongst these, long non-coding RNAs (lncRNAs), a subclass of non-coding RNAs typically longer than 200 nucleotides, have been shown to participate in brain development and function, and the dysregulation of their expression implicated in many neurological disorders [ 29 ]. In particular, aberrant expression of many lncRNAs has been linked to AD [ 30 , 31 ]. To date, it remains unclear if and how lncRNAs influence AD development and progression.…”

“…Several lncRNAs are aberrantly expressed in AD brains compared to healthy controls, suggesting a strong association between altered lncRNA expression and AD pathology ( Table 2 ) [ 30 , 31 ]. Although a direct contribution to AD pathology of many of these lncRNAs remains unknown, multiple studies have shown their implication in AD-related pathways including Aβ and Tau production and/or clearance, autophagy, neuronal proliferation, and apoptosis [ 31 ].…”