Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10842913 | Progress in Lipid Research | 2013 | 18 Pages |
Abstract
Cannabinoids, the active components of cannabis (Cannabis sativa) extracts, have attracted the attention of human civilizations for centuries, much earlier than the discovery and characterization of their substrate of action, the endocannabinoid system (ECS). The latter is an ensemble of endogenous lipids, their receptors [in particular type-1 (CB1) and type-2 (CB2) cannabinoid receptors] and metabolic enzymes. Cannabinoid signaling regulates cell proliferation, differentiation and survival, with different outcomes depending on the molecular targets and cellular context involved. Cannabinoid receptors are expressed and functional from the very early developmental stages, when they regulate embryonic and trophoblast stem cell survival and differentiation, and thus may affect the formation of manifold adult specialized tissues derived from the three different germ layers (ectoderm, mesoderm and endoderm). In the ectoderm-derived nervous system, both CB1 and CB2 receptors are present in neural progenitor/stem cells and control their self-renewal, proliferation and differentiation. CB1 and CB2 show opposite patterns of expression, the former increasing and the latter decreasing along neuronal differentiation. Recently, endocannabinoid (eCB) signaling has also been shown to regulate proliferation and differentiation of mesoderm-derived hematopoietic and mesenchymal stem cells, with a key role in determining the formation of several cell types in peripheral tissues, including blood cells, adipocytes, osteoblasts/osteoclasts and epithelial cells. Here, we will review these new findings, which unveil the involvement of eCB signaling in the regulation of progenitor/stem cell fate in the nervous system and in the periphery. The developmental regulation of cannabinoid receptor expression and cellular/subcellular localization, together with their role in progenitor/stem cell biology, may have important implications in human health and disease.
Keywords
NCAM2-AGmaglpKaNGFeCB2-arachidonoylglycerolFAAHmGluRSVZGSK3βPI3KVGLUTICMCBGmTORC1CFU-GEMMN-PalmitoylethanolamineN-oleoylethanolamineN-arachidonoylethanolamineL1-CAMRANKLCBDFGFERKTHCHPCPEAGADAEAHSCCREBPPARγBDNFcannabigerolECsDAGLOEAΔ9-TetrahydrocannabinolendocannabinoidFatty acid amide hydrolaseendocannabinoidsCell survivalCell commitmentInner cell massvesicular glutamate transporterembryonic stemhematopoietic stem cellsHematopoietic progenitor cellsendocannabinoid systembrain derived neurotrophic factorColony-stimulating factorsTranscription factorsnerve growth factorfibroblast growth factorPhosphoinositol 3-kinasemonoacylglycerol lipasediacylglycerol lipaseCSFventricular zonesubventricular zoneneural cell adhesion moleculeMammalian target of rapamycin complex 1cAMP response element-binding proteinprotein kinasesProtein kinase-ACannabidiolGlutamate decarboxylaseMembrane receptorsperoxisome proliferator activated receptorsMetabotropic glutamate receptorsreceptor activator of nuclear factor kappa-B ligand
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Authors
Ismael Galve-Roperh, Valerio Chiurchiù, Javier DÃaz-Alonso, Monica Bari, Manuel Guzmán, Mauro Maccarrone,