title: tCFA15, a trimethyl cyclohexenonic long-chain fatty alcohol, affects neural stem fate and differentiation by modulating Notch1 activity.
abstract: We have investigated the effects of tCFA15, a non-peptidic compound, on the differentiation of neural stem cell-derived neurospheres, and have found that tCFA15 promotes their differentiation into neurons and reduces their differentiation into astrocytes, in a dose-dependent manner. This response is reminiscent of that resulting from the loss-of-function of Notch signaling after inactivation of the Delta-like 1 (Dll1) gene. Further analysis of the expression of genes from the Notch pathway by reverse transcriptase-PCR revealed that tCFA15 treatment results in a consistent decrease in the level of Notch1 mRNA. We have confirmed this result in other cell lines and propose that it reflects a general effect of the tCFA15 molecule. We discuss the implications of this finding with respect to regulation of Notch activity in neural stem cells, and the possible use of tCFA15 as a therapeutic tool for various pathologies that result from impairment of Notch signaling.
authors: CNRS, UPR 3212, INCI, 5 rue Blaise Pascal, 67084 Strasbourg, France.
authors: Julien
authors: J
authors: Bouissac
authors: Jeremy
authors: J
authors: Garwood
authors: Céline
authors: C
authors: Girlanda-Jungès
authors: Bang
authors: B
authors: Luu
authors: Pascal
authors: P
authors: Dollé
authors: Eliane
authors: E
authors: Mohier
authors: Marie
authors: M
authors: Paschaki
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D003512:Cyclohexanones / Q000494:pharmacology*; D005233:Fatty Alcohols / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C420963:3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen-1-one; D003512:Cyclohexanones; D005233:Fatty Alcohols; D012333:RNA, Messenger; D051881:Receptor, Notch1
keywords: Brain; Neural stem cell; Neuronal differentiation; Neurosphere; Notch signaling