Alzheimer’s Disease and ncRNAs

Abstract

Alzheimer's disease is a devastating neurodegenerative disorder affecting a significant portion of the world's rapidly growing aging population. In spite of its prevalence, the etiology of the disease is still poorly understood, and effective therapy is all but unavailable. Over the past decade, noncoding RNA, including microRNA (miRNA), has emerged as a major class of regulatory molecules involved in virtually all physiological and disease states. The specificity provided by miRNA sequence complementarity, together with the ability of these molecules to regulate complex networks of genes, has made them exciting novel targets for therapeutic agents. In this chapter, we review recent progress on understanding the role of noncoding RNA in Alzheimer's disease (AD). The majority of available work has focused on miRNA, and we review the many studies implicating specific miRNAs in the development of the disease. More recently, several studies have tied other RNA classes to the disorder, including long noncoding RNA, circular RNA, and Y RNAs, and we review this fascinating field as well. Finally, we explore the potential promise of these findings for future therapeutic applications.

Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain

“…The structure, function and evolution of miRNAs including their expanding list of critical regulatory roles in CNS development and age-related human neurodegenerative diseases such as AD have been extensively reviewed and will not be dealt with further here [1,2,34,41,45,49,51,70,83,88]. Because miRNAs are relatively unstable in brain and retinal tissues with half-lives on the order of ~1-3 hrs, only significantly up-regulated miRNAs have been studied in short post-mortem interval (PMI) tissues of PMIs of 2-3 hrs or less; down-regulated miRNAs may simply be a consequence of the highly oxidative and pro-inflammatory degradative environment of actively degenerating neural tissues [11,59,67].…”

Cholino‐ncRNAs modulate sex‐specific‐ and age‐related acetylcholine signals

“…In this review, we aimed to illuminate the important and complex role of ncRNAs in orchestrating the cholinergic tone, and to highlight the fact that there is still much to look forward to. For example, a rapidly growing body of evidence shows that among other agents, circular RNAs can also operate as sponges [42]. Additionally, transfer RNA fragments, a recently identified family of short ncRNAs that may operate as expression regulators via sequence-specific transcript degradation, emerge as active regulators of multiple biological processes [93,94].…”

“…Other lncRNAs are abundantly localized in the cytoplasm and operate as 'sponges' for short RNAs [30]. Thanks to their large number, certain lncRNAs play important roles in controlling cellular gene expression at large [31,41] and ACh signaling in particular [42,43], while others are being studied in different contexts.…”

Loss of miR-369 Promotes Tau Phosphorylation by Targeting the Fyn and Serine/Threonine-Protein Kinase 2 Signaling Pathways in Alzheimer’s Disease Mice

“…Over the years, expression profiling of miRNAs associated with AD has been performed in the brain tissues, cerebrospinal fluid, and blood of AD patients and transgenic AD mouse models. Although several miRNAs have been identified in AD, an understanding of the role of miRNA in human AD is still limited (Tan et al, 2013;Maoz et al, 2017;Quinlan et al, 2017). miRNAs may be involved in AD pathogenesis via multiple pathways, such as APP formation, phosphorylation of tau protein, and synaptic plasticity.…”