Bouissac Julien, Garwood Jeremy, Girlanda-Jungès Céline, Luu Bang, Dollé Pascal, Mohier Eliane, Paschaki Marie
CNRS, UPR 3212, INCI, 5 rue Blaise Pascal, 67084 Strasbourg, France.
Eur J Pharmacol. 2013 Oct 15;718(1-3):383-92. doi: 10.1016/j.ejphar.2013.08.005. Epub 2013 Aug 24.
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.
我们研究了非肽类化合物tCFA15对神经干细胞来源的神经球分化的影响，发现tCFA15以剂量依赖的方式促进其向神经元分化，并减少其向星形胶质细胞的分化。这种反应让人联想到Delta样1（Dll1）基因失活后Notch信号功能丧失所产生的反应。通过逆转录聚合酶链反应对Notch途径基因表达的进一步分析表明，tCFA15处理导致Notch1 mRNA水平持续下降。我们在其他细胞系中证实了这一结果，并提出这反映了tCFA15分子的普遍作用。我们讨论了这一发现对神经干细胞中Notch活性调节的意义，以及tCFA15作为治疗因Notch信号受损导致的各种疾病的治疗工具的可能性。
