Non-Coding RNAs as Novel Regulators of Neuroinflammation in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is one of the most common causes of dementia. Although significant breakthroughs have been made in understanding the progression and pathogenesis of AD, it remains a worldwide problem and a significant public health burden. Thus, more efficient diagnostic and therapeutic strategies are urgently required. The latest research studies have revealed that neuroinflammation is crucial in the pathogenesis of AD. Non-coding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), and transfer RNA-derived small RNAs (tsRNAs), have been strongly associated with AD-induced neuroinflammation. Furthermore, several ongoing pre-clinical studies are currently investigating ncRNA as disease biomarkers and therapeutic interventions to provide new perspectives for AD diagnosis and treatment. In this review, the role of different types of ncRNAs in neuroinflammation during AD are summarized in order to improve our understanding of AD etiology and aid in the translation of basic research into clinical practice.

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

“…A recent review, while we were in the revision process, has highlighted the role of non-coding RNA, in regulating inflammation in AD [ 54 ]. In that manuscript, only proinflammatory lncRNA is described.…”

Current advances in our understanding of circular RNA (circRNA) in Alzheimer’s disease (AD); the potential utilization of synthetic circRNAs as a therapeutic strategy in the clinical management of AD

“…Fourthly, circRNAs containing miRNA-type sequences have potential to target multiple mRNAs and hence multiple highly interactive gene expression pathways, and several mRNAs may be targeted and down-regulated by multiple interdependent circRNA-containing miRNA or AM species (Zhao et al, 2016;Bartel, 2018;Pogue and Lukiw, 2018;Nguyen et al, 2021). Fifthly circRNAs are immunologically well-tolerated in multiple cellular systems into which they have been introduced, probably because they are a naturallyoccurring form of nucleic acid and their lack of free 3′ or 5′ termini enables circRNAs to escape from RNA-mediated host immune responses (Liu et al, 2022;.…”

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

“…Accumulated evidence indicates that neuroinflammation in different brain areas is a common denominator in several degenerative disorders of various etiology, e.g. Huntington's disease [2], Parkinson's disease (PD) [3] and Alzheimer's disease (AD) [4], [5]. In AD, the association of amyloid plaques (Aβ) deposits and tau neurofibrillary tangles (NFT) with neuroinflammation has been extensively acknowledged [6][7] [8]- [10] to the point that immunotherapies have been proposed to ameliorate AD [11].…”