Role of CD36 in central nervous system diseases

CD36 is a highly glycosylated integral membrane protein that belongs to the scavenger receptor class B family and regulates the pathological progress of metabolic diseases.CD36 was recently found to be widely expressed in various cell types in the nervous system,including endothelial cells,pericytes,astrocytes,and microglia.CD36 mediates a number of regulatory processes,such as endothelial dysfunction,oxidative stress,mitochondrial dysfunction,and inflammatory responses,which are involved in many central nervous system diseases,such as stroke,Alzheimer’s disease,Parkinson’s disease,and spinal cord injury.CD36 antagonists can suppress CD36 expression or prevent CD36 binding to its ligand,thereby achieving inhibition of CD36-mediated pathways or functions.Here,we reviewed the mechanisms of action of CD36 antagonists,such as Salvianolic acid B,tanshinone IIA,curcumin,sulfosuccinimidyl oleate,antioxidants,and small-molecule compounds.Moreover,we predicted the structures of binding sites between CD36 and antagonists.These sites can provide targets for more efficient and safer CD36 antagonists for the treatment of central nervous system diseases.

RNA sequencing of exosomes secreted by fibroblast and Schwann cells elucidates mechanisms underlying peripheral nerve regeneration

Exosomes exhibit complex biological functions and mediate a variety of biological processes,such as promoting axonal regeneration and functional recove ry after injury.Long non-coding RNAs(IncRNAs)have been reported to play a crucial role in axonal regeneration.Howeve r,the role of the IncRNA-microRNAmessenger RNA(mRNA)-competitive endogenous RNA(ceRNA)network in exosome-mediated axonal regeneration remains unclear.In this study,we performed RNA transcriptome sequencing analysis to assess mRNA expression patterns in exosomes produced by cultured fibroblasts(FC-EXOs)and Schwann cells(SCEXOs).Diffe rential gene expression analysis,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and protein-protein intera ction network analysis were used to explo re the functions and related pathways of RNAs isolated from FC-EXOs and SC-EXOs.We found that the ribosome-related central gene Rps5 was enriched in FC-EXOs and SC-EXOs,which suggests that it may promote axonal regeneration.In addition,using the miRWalk and Starbase prediction databases,we constructed a regulatory network of ceRNAs targeting Rps5,including 27 microRNAs and five IncRNAs.The ceRNA regulatory network,which included Ftx and Miat,revealed that exsosome-derived Rps5 inhibits scar formation and promotes axonal regeneration and functional recovery after nerve injury.Our findings suggest that exosomes derived from fibro blast and Schwann cells could be used to treat injuries of peripheral nervous system.

Spatiotemporal Dynamics of the Molecular Expression Pattern

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors–the glial scar is triggered by injury and inhibits or promotes regeneration.Recent technological advances in spatial transcriptomics(ST)provide a unique opportunity to decipher most genes systematically throughout scar formation,which remains poorly understood.Here,we frst constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples.Locally,we profled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment,such as neurotransmitter disorders,activation of the pro-infammatory response,neurotoxic saturated lipids,angiogenesis,obstructed axon extension,and extracellular structure re-organization.In addition,we described 21 cell transcriptional states during scar formation and delineated the origins,functional diversity,and possible trajectories of subpopulations of fbroblasts,glia,and immune cells.Specifcally,we found some regulators in special cell types,such as Thbs1 and Col1a2 in macrophages,CD36 and Postn in fbroblasts,Plxnb2 and Nxpe3 in microglia,Clu in astrocytes,and CD74 in oligodendrocytes.Furthermore,salvianolic acid B,a blood–brain barrier permeation and CD36 inhibitor,was administered after surgery and found to remedy fbrosis.Subsequently,we described the extent of the scar boundary and profled the bidirectional ligand-receptor interactions at the neighboring cluster boundary,contributing to maintain scar architecture during gliosis and fbrosis,and found that GPR37L1_PSAP,and GPR37_PSAP were the most signifcant gene-pairs among microglia,fbroblasts,and astrocytes.Last,we quantifed the fraction of scar-resident cells and proposed four possible phases of scar formation:macrophage infltration,proliferation and diferentiation of scar-resident cells,scar emergence,and scar stationary.Together,these profles delineated the spatial heterogeneity of the scar,confrmed the previous concepts about scar architecture,provided some new clues for scar formation,and served as a valuable resource for the treatment of central nervous system injury.