Exosomal noncoding RNAs in central nervous system diseases: biological functions and potential clinical applications

Abstract

Central nervous system (CNS) disease is a general term for a series of complex and diverse diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), CNS tumors, stroke, epilepsy, and amyotrophic lateral sclerosis (ALS). Interneuron and neuron-glia cells communicate with each other through their homeostatic microenvironment. Exosomes in the microenvironment have crucial impacts on interneuron and neuron-glia cells by transferring their contents, such as proteins, lipids, and ncRNAs, constituting a novel form of cell-to-cell interaction and communication. Exosomal noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and PIWI-interacting RNAs (piRNAs), regulate physiological functions and maintain CNS homeostasis. Exosomes are regarded as extracellular messengers that transfer ncRNAs between neurons and body fluids due to their ability to cross the blood-brain barrier. This review aims to summarize the current understanding of exosomal ncRNAs in CNS diseases, including prospective diagnostic biomarkers, pathological regulators, therapeutic strategies and clinical applications. We also provide an all-sided discussion of the comparison with some similar CNS diseases and the main limitations and challenges for exosomal ncRNAs in clinical applications.

Key developments and hotspots of exosomes in Alzheimer’s disease: a bibliometric study spanning 2003 to 2023

“…Numerous RNAs can be employed as biomarkers for the diagnosis, management, and prognosis of AD. Wang Z. Y. et al (2022) summarized various functions of exosomal noncoding RNAs in AD in a review published in Frontiers in molecular neuroscience in 2022 and found that different RNAs have different roles in affecting the elimination and accumulation of Aβ, APP and tau, which can be used as good pathological modulators and biomarkers. MiRNA has the largest number of non-coding RNA subtypes.…”

The Potential of Targeting Autophagy-Related Non-coding RNAs in the Treatment of Alzheimer’s and Parkinson’s Diseases

“…The development of reliable for diagnosing early neurodegeneration and its molecular signaling will be pivotal for increased efficiency of therapies. Some studies evaluated targeting and transcriptionally repressing ncRNAs by silencing ncRNAs and RNA interference to inhibit ncRNAs expression in neurodegenerative disorders (Wang et al 2022 ; Zhang et al 2021b ). Moreover, CRISPRs could be applied to delete miRNAs/lncRNAs (Ho et al 2015 ) and assess the consequences for therapeutic strategies.…”

Circular RNA in Multiple Sclerosis: Pathogenicity and Potential Biomarker Development: A Systematic Review

“…While a search for circRNA in MS yielded 16 review papers, none of them discussed the role of circRNA in MS as comprehensively as this review. Some of these papers barely mentioned circRNA, 64,[86][87][88][89][90][91][92] while others focused on other types of ncRNAs such as miRNA and LncRNA. 93,94 A few papers discussed the role of circRNA in other types of diseases but did not mention MS. [95][96][97][98] The lack of comprehensive discussion on the role of circRNA in MS and other diseases may be attributed to the limited understanding of this molecule.…”