Interactions between microglia and glioma in tumor microenvironment.

Gliomas, the most prevalent primary tumors in the central nervous system, are marked by their immunosuppressive properties and consequent poor patient prognosis. Current evidence emphasizes the pivotal role of the tumor microenvironment in the progression of gliomas, largely attributed to tumor-associated macrophages (brain-resident microglia and bone marrow-derived macrophages) that create a tumor microenvironment conducive to the growth and invasion of tumor cells. Yet, distinguishing between these two cell subgroups remains a challenge. Thus, our review starts by analyzing the heterogeneity between these two cell subsets, then places emphasis on elucidating the complex interactions between microglia and glioma cells. Finally, we conclude with a summary of current attempts at immunotherapy that target microglia. However, given that independent research on microglia is still in its initial stages and has many shortcomings at the present time, we express our related concerns and hope that further research will be carried out to address these issues in the future.

Gas5 inhibition promotes the axon regeneration in the adult mammalian nervous system.

Neurons in the peripheral nervous system (PNS) have robust regenerative capacity after axon injury, but the regenerative capacity is generally absent in the neurons of the central nervous system (CNS) in mammals. Increasing evidence highlighted the pivotal roles of long-noncoding RNAs (lncRNAs) in development and disease, but the role of LncRNA in triggering the regenerative capacity in CNS and PNS is not well studied. Here, we reported that lncRNA Gas5 is a suppressor for axon regeneration. Bioinformatics analysis shows that Gas5 is age-dependent up-regulated during DRG neurons development and down-regulated after sciatic nerve injury. In vitro, inhibiting the expression of Gas5 promotes the neurite growth of DRG neurons both in mice and rats. Consistently, Gas5 overexpression inhibits axon growth of mice DRG neurons. In vivo, Gas5 knockout(Gas5-/-) mice display enhanced nerve regeneration ability after sciatic nerve injury. RNA pull-down analysis indicates that Gas5 can interacts with soluble Vimentin, which is essential for peripheral nerve development and regeneration. Vimentin knockdown reverses the Gas5 silence-regulated axon pro-regeneration demonstrating that the function of Gas5 depending on Vimentin. Besides, inhibition of Gas5 expression can also enhance optic nerve regeneration indicating a potential pro-regenerative ability of Gas5 silence in CNS. Our study for the first time provides direct evidence in vivo that lncRNA plays a role in regulating central axon regrowth and Gas5 might be a novel therapeutic target for axon regeneration in both PNS and CNS.

Unfolded protein response-induced expression of long noncoding RNA Ngrl1 supports peripheral axon regeneration by activating the PI3K-Akt pathway.

In mammals, long noncoding RNA (LncRNA) contributes to neuronal development and injury repair mediated by the spatiotemporal regulation of gene expression. However, the pivotal role of lncRNA in intrinsic axon regeneration control following a nerve injury remains unknown. In this article, we report a neurite growth-related lncRNA termed Ngrl1, which supported peripheral axon regeneration post sciatic nerve crush (SNC). A rapid increase in Ngrl1 expression was detected following SNC, and knockdown of Ngrl1 impaired axon regeneration both in vitro and in vivo. The unfolded protein response (i.e., the upstream modulator of Ngrl1 expression) improved the impairment of neurite growth induced by Ngrl1 inhibition in matured dorsal root ganglion neurons. Meanwhile, interference with Ngrl1 impacts the PI3K-Akt pathway, leading to a marked decrease in Akt phosphorylation. Furthermore, the activation of Akt by insulin-like growth factor 1 (IGF-1) or SC79 reversed the reduction of axon regeneration in dorsal root ganglion neuron following inhibition of Ngrl1. In conclusion, unfolded protein response-induced Ngrl1 expression supports the intrinsic control of peripheral axon regeneration by modulating the activation of the PI3K-Akt pathway following SNC.