Abstract
Exosomes are small bilipid layer-enclosed extracellular vesicles that can be found in tissues and biological fluids. As a key cell-to-cell and distant communication mediator, exosomes are involved in various central nervous system (CNS) diseases, potentially through transferring their contents such as proteins, lipids and nucleic acids to the target cells. Exosomal miRNAs, which are small non-coding RNAs in the exosomes, are known to be more stable than free miRNAs and therefore have lasting effects on disease-related gene expressions. There are distinct profiles of exosomal miRNAs in different types of CNS diseases even before the onset of irreversible neurological damages, indicating that exosomal miRNAs within tissues and biological fluids could serve as promising biomarkers. Emerging evidence has also demonstrated the pathological effects of several exosomal miRNAs in CNS diseases via specific modulation of disease-related factors. Moreover, exosomes carry therapeutically beneficial miRNAs across the blood-brain-barrier, which can be exploited as a powerful drug delivery tool to help alleviating multiple CNS diseases. In this review, we summarize the recent progress made in understanding the biological roles of exosomal miRNAs as potential diagnostic biomarkers, pathological regulators, and therapeutic targets/drugs for CNS diseases. A comprehensive discussion of the main concerns and challenges for the applications of exosomal miRNAs in the clinical setting is also provided.
Highlights
Intercellular communication is crucial for the proper functions of the central nervous system (CNS) in all multi-cellular organisms
Though no receiver operating characteristic (ROC) analyses were done and larger sizes of samples should be recruited for validation purpose, these significantly differentially expressed exosomal miRNAs may serve as a potential prognostic indicator for therapy response or even become a therapeutic target to enhance the curative effect of existing drugs
As a newly developed research field, the roles and mechanisms of exosomal miRNAs in CNS diseases are under extensive investigation
Summary
Intercellular communication is crucial for the proper functions of the central nervous system (CNS) in all multi-cellular organisms. Though no current study reported the dysregulation of these RNA-binding proteins, the abnormal abundance of their targets (e.g. miR-223) in CNS disorder patients’ serum exosomes was observed These findings indicate that these miRNA sorting mechanisms during exosome biogenesis may be interrupted in the pathogenesis and neuroregeneration of CNS disorders (e.g. stoke) (Chen et al, 2017b). Neural-derived exosomes (NDE) can be isolated from plasma using a combined approach of precipitation and immunoadsorption that targets L1 cell adhesion molecule (L1CAM), which is expressed on neurons (Fiandaca et al, 2015; Goetzl et al, 2015b) This strategy has been used to identify AD-related proteins amyloid beta (Aβ) and forms of tau ( p-tau) in NDE that distinguish cognitively normal controls from patients with frontotemporal dementia or AD (Fiandaca et al, 2015). We will only discuss the roles of exosomal miRNAs (not cellular or free miRNAs) as biomarkers, pathological mediator, therapeutic targets, and “drug” delivered by modified exosomes for CNS diseases due to their unique properties
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