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.
Patients with Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI), stroke, and postoperative neurocognitive disorder (POND) are commonly faced with neurocognitive disorders with limited therapeutic options. Some non-coding ribonucleic acids (ncRNAs) are involved in the development of various brain cognitive disorders. Circular RNAs (circRNAs), a typical group of ncRNAs, can function as competitive endogenous RNAs (ceRNAs) to dysregulate shared microRNAs (miRNAs) at post-transcription level, inhibiting regulation of miRNAs on their targeted messenger RNAs (mRNAs). circRNAs are abundant in central nervous system (CNS) diseases and cause brain disorders, but the exact roles of circRNAs are unclear. The crosstalk between circRNA, miRNA, and mRNA plays an important role in the pathogenesis of these neurocognitive dysfunction diseases and abnormal conditions including AD, PD, stroke, TBI, and POND. In this review, we summarized the participation of circRNA in neuroglial damage and inflammation. Finally, we aimed to highlight the regulatory mechanisms of circRNA–miRNA–mRNA networks in the development of various brain cognitive disorders and provide new insights into the therapeutics of these diseases.