title: Modulation of the Isoprenoid/Cholesterol Biosynthetic Pathway During Neuronal Differentiation In Vitro.
abstract: During differentiation, neurons acquire their typical shape and functional properties. At present, it is unclear, whether this important developmental step involves metabolic changes. Here, we studied the contribution of the mevalonate (MVA) pathway to neuronal differentiation using the mouse neuroblastoma cell line N1E-115 as experimental model. Our results show that during differentiation, the activity of 3-hydroxy 3-methylglutaryl Coenzyme A reductase (HMGR), a key enzyme of MVA pathway, and the level of Low Density Lipoprotein receptor (LDLr) decrease, whereas the level of LDLr-related protein-1 (LRP1) and the dimerization of Scavanger Receptor B1 (SRB-1) rise. Pharmacologic inhibition of HMGR by simvastatin accelerated neuronal differentiation by modulating geranylated proteins. Collectively, our data suggest that during neuronal differentiation, the activity of the MVA pathway decreases and we postulate that any interference with this process impacts neuronal morphology and function. Therefore, the MVA pathway appears as an attractive pharmacological target to modulate neurological and metabolic symptoms of developmental neuropathologies. J. Cell. Biochem. 117: 2036-2044, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Science, Biomedical and Technology Science Section, University Roma Tre, Viale Marconi, 446, 00146, Rome, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Cartocci
authors.affiliation: Department of Biosciences, University of Milan, Via Giovanni Celoria, 26, 20133, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Segatto
authors.affiliation: Department of Science, Biomedical and Technology Science Section, University Roma Tre, Viale Marconi, 446, 00146, Rome, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Di Tunno
authors.affiliation: Department of Science, Biomedical and Technology Science Section, University Roma Tre, Viale Marconi, 446, 00146, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Leone
authors.affiliation: Institute of Cellular and Integrative Neurosciences (INCI) CNRS UPR 3212, University of Strasbourg, 5 rue Blaise Pascal, 67084, Strasbourg, France.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Pfrieger
authors.affiliation: Department of Science, Biomedical and Technology Science Section, University Roma Tre, Viale Marconi, 446, 00146, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Pallottini
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000096:biosynthesis* / Q000235:genetics; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent / Q000235:genetics / Q000378:metabolism; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology; D013729:Terpenes / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D011973:Receptors, LDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013729:Terpenes; D025521:Tumor Suppressor Proteins; D002784:Cholesterol; D019821:Simvastatin; D025782:Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent
keywords: 3-HYDROXY 3-METHYLGLUTARYL COENZYME A REDUCTASE; CHOLESTEROL; ISOPRENOID; LIPOPROTEIN RECEPTORS; N1E-115; NEURONAL DIFFERENTIATION