tCFA15, a trimethyl cyclohexenonic long-chain fatty alcohol, affects neural stem fate and differentiation by modulating Notch1 activity

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.

Keywords: Brain; Neural stem cell; Neuronal differentiation; Neurosphere; Notch signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Cell Differentiation / drug effects*
  • Cyclohexanones / pharmacology*
  • Fatty Alcohols / pharmacology*
  • Gene Expression Regulation / drug effects
  • Mice
  • Neural Stem Cells / cytology*
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*


  • 3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen-1-one
  • Cyclohexanones
  • Fatty Alcohols
  • RNA, Messenger
  • Receptor, Notch1