Exosomal miRNAs in central nervous system diseases: biomarkers, pathological mediators, protective factors and...

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.