As a class of important endogenous small noncoding RNAs that regulate gene expression at the posttranscriptional level, microRNAs (miRNAs) play a critical role in many physiological and pathological processes. It is believed that miRNAs contribute to the development, differentiation, and synaptic plasticity of the neurons, and their dysregulation has been linked to a series of diseases. MiRNAs exist in the tissues and as circulating miRNAs in several body fluids, including plasma or serum, cerebrospinal fluid, urine, and saliva. There are significant differences between the circulating miRNA expression profiles of healthy individuals and those of patients. Consequently, circulating miRNAs are likely to become a novel class of noninvasive and sensitive biomarkers. Although little is known about the origin and functions of circulating miRNAs at present, their roles in the clinical diagnosis and prognosis of diseases make them attractive markers, particularly for tumors and cardiovascular diseases. Until now, however, there have been limited data regarding the roles of circulating miRNAs in central nervous system (CNS) diseases. This review focuses on the characteristics of circulating miRNAs and their values as potential biomarkers in CNS diseases, particularly in Alzheimer's disease, Huntington's disease, multiple sclerosis, schizophrenia, and bipolar disorder.
Endosomal Toll-like receptors (TLRs) mediate intracellular innate immunity via the recognition of DNA and RNA sequences. Recent work has reported a role for extracellular vesicles (EVs), known to transfer various nucleic acids, in uptake of TLR-activating molecules, raising speculation about possible roles of EVs in innate immune surveillance. Whether EV-mediated uptake is a general mechanism, however, was unresolved; and the molecular machinery that might be involved was unknown. We show that, when macrophages are stimulated with the TLR9 agonist CpG oligodeoxynucleotides (ODN), the secreted EVs transport ODN into naïve macrophages and induce the release of chemokine TNF-α. In addition, these EVs transfer Cdc42 into recipient cells, resulting in further enhancement of their cellular uptake. Transport of ODN and Cdc42 from TLR9-activated macrophages to naïve cells via EVs exerts synergetic effects in propagation of the intracellular immune response, suggesting a general mechanism of EV-mediated uptake of pathogen-associated molecular patterns.
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