Central nervous system (CNS) diseases, such as multiple sclerosis, Alzheimer's disease (AD), and Parkinson’s disease (PD), affect millions of people around the world. Great efforts were put in disease related research, but few breakthroughs have been made in the diagnostic and therapeutic approaches. Exosomes are cell-derived extracellular vesicles containing diverse biologically active molecules secreted by their cell of origin. These contents, including nucleic acids, proteins, lipids, amino acids, and metabolites, can be transferred between different cells, tissues, or organs, regulating various intercellular cross-organ communications and normal and pathogenic processes. Considering that cellular environment and cell state strongly impact the content and uptake efficiency of exosomes, their detection in biological fluids and content composition analysis potentially offer a multicomponent diagnostic readout of several human diseases. Recently, studies have found that aberrant secretion and content of exosomes are closely related to the pathogenesis of CNS diseases. Besides, loading natural cargoes, exosomes can deliver drugs cross the blood brain barrier, making them emerging candidates of biomarkers and therapeutics for CNS diseases. In this review, we summarize and discuss the advanced research progress of exosomes in the pathological processes of several CNS diseases in regarding with neuroinflammation, CNS repair, and pathological protein aggregation. Moreover, we propose the therapeutic strategies of applying exosomes to the diagnosis, early detection, and treatment of CNS diseases.

Background: Receptor-interacting protein 3 (RIP3), a member of RIP family proteins, has been shown to participate in programmed necrosis or necroptosis in cell biology studies. Evidence suggests that necroptosis may be a mode of neuronal death in the retina.Results: In the present study we determined the expression of RIP3 in normal rat retina and its changes following acute high intraocular pressure (aHIOP). RIP3 immunoreactivity (IR) was largely present in the inner retinal layers, localized to subsets of cells expressing neuron-specific nuclear antigen (NeuN), parvalbumin and calbindin in the ganglion cell layer (GCL) and inner nuclear layer (INL). No double labeling was detected for RIP3 with PKC-α or rhodopsin. RIP3 immunoreactivity was increased in the GCL at 6 hr and 12 hr, but reduced at 24 hr in the retina, without apparent alteration in laminar or cellular distribution pattern. Western blot analysis confirmed the above time-dependent alteration in RIP3 protein expression. RIP3 expressing cells frequently co-localized with propidium iodide (PI). A few co-localized cells were observed between RIP3 and Bax or cleaved caspase-3 in the GCL in 12 hr following aHIOP.Conclusions: The results indicate that RIP3 is expressed differentially in retinal neurons in adult rats, including subsets of ganglion cells, amacrine and horizontal cells. RIP3 protein levels are elevated rapidly following aHIOP. RIP3 labeling co-localized with PI, Bax or cleaved caspase-3 among cells in the ganglion cell layer following aHIOP, which suggest its involvement of RIP3 in neuronal responses to acute ischemic insults.

N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells, which participates in the functional regulation of various biological processes. It regulates the expression of targeted genes by affecting RNA translocation, alternative splicing, maturation, stability, and degradation. As recent evidence shows, of all organs, brain has the highest abundance of m6A methylation of RNAs, which indicates its regulating role in central nervous system (CNS) development and the remodeling of the cerebrovascular system. Recent studies have shown that altered m6A levels are crucial in the aging process and the onset and progression of age-related diseases. Considering that the incidence of cerebrovascular and degenerative neurologic diseases increase with aging, the importance of m6A in neurological manifestations cannot be ignored. In this manuscript, we focus on the role of m6A methylation in aging and neurological manifestations, hoping to provide a new direction for the molecular mechanism and novel therapeutic targets.

Background: Brain microvascular endothelial cell (BMEC) injury can affect neuronal survival by modulating immune responses through the microenvironment. Exosomes are important vehicles of transport between cells. However, the regulation of the subtypes of microglia by BMECs through the exosome transport of microRNAs (miRNAs) has not been established. Methods: In this study, exosomes from normal and oxygen–glucose deprivation (OGD)-cultured BMECs were collected, and differentially expressed miRNAs were analyzed. BMEC proliferation, migration, and tube formation were analyzed using MTS, transwell, and tube formation assays. M1 and M2 microglia and apoptosis were analyzed using flow cytometry. miRNA expression was analyzed using real-time polymerase chain reaction (RT-qPCR), and IL-1β, iNOS, IL-6, IL-10, and RC3H1 protein concentrations were analyzed using western blotting. Results: We found that miR-3613-3p was enriched in BMEC exosome by miRNA GeneChip assay and RT-qPCR analysis. miR-3613-3p knockdown enhanced cell survival, migration, and angiogenesis in the OGD-treated BMECs. In addition, BMECs secrete miR-3613-3p to transfer into microglia via exosomes, and miR-3613-3p binds to the RC3H1 3′ untranslated region (UTR) to reduce RC3H1 protein levels in microglia. Exosomal miR-3613-3p promotes microglial M1 polarization by inhibiting RC3H1 protein levels. BMEC exosomal miR-3613-3p reduces neuronal survival by regulating microglial M1 polarization. Conclusions: miR-3613-3p knockdown enhances BMEC functions under OGD conditions. Interfering with miR-3613-3p expression in BMSCs reduced the enrichment of miR-3613-3p in exosomes and enhanced M2 polarization of microglia, which contributed to reduced neuronal apoptosis.

Purpose: Long intergenic noncoding RNA 01121 (LINC01121) has been reported to be aberrantly expressed and acts as an oncogene in pancreatic cancer. However, the detailed molecular mechanism of LINC01121 in breast cancer remains largely unclear. In this study, we aimed to investigate the expression and biological function of LINC01121 in breast cancer. Methods: LINC01121 and miR-150-5p expression were measured in breast cancer cell lines using quantitative reverse transcription PCR. MTS and flow cytometry assays were performed to determine cell proliferation, the cell cycle, and apoptosis. Cell migration and invasion were assessed by transwell assay. The protein expression of HMGA2 in breast cancer cell lines was measured by Western blotting. A luciferase reporter assay was used to assess the binding of LINC01121 and miR-150-5p. Results: We found that LINC01121 was markedly up-regulated in breast cancer cell lines compared with normal breast epithelial cells. LINC01121 down-regulation markedly suppressed cell proliferation, cell cycle progression, migration, and invasion and promoted apoptosis in breast cancer cells. Further investigation showed that LINC01121 could serve as a molecular sponge for miR-150-5p and indirectly modulate the expression of its target, HMGA2. Moreover, miR-150-5p knockdown rescued the effects of LINC01121 down-regulation on HMGA2 protein expression, cell proliferation, cell cycle progression, apoptosis, migration, and invasion in breast cancer cells. Conclusion: Knockdown LINC01121 inhibited breast cancer cell proliferation, migration, and invasion via the miR-150-5p/HMGA2 axis.

Iron is one of the most crucial elements in the human body. In recent years, a kind of programmed, non-apoptotic cell death closely related to iron metabolism-called ferroptosis- has aroused much interest among many scientists. Ferroptosis also interacts with other pathways involved in cell death including iron abnormality, the cystine/glutamate antiporter and lipid peroxidation. Together these pathological pathways exert great impacts on intracerebral hemorrhage (ICH), a lethal cerebrovascular disease with a high incidence rate and mortality rate. Furthermore, the ferroptosis also affects different brain cells (neurons and neuroglial cells) and different organelles (mitochondria and endoplasmic reticulum). Clinical treatments for ferroptosis in ICH have been closely investigated recently. This perspective provides a comprehensive summary of ferroptosis mechanisms after ICH and its interaction with other cell death patterns. Understanding the role of ferroptosis in ICH will open new windows for the future treatments and preventions for ICH and other intracerebral diseases.