Effects of indole fatty alcohols on the differentiation of neural stem cell derived neurospheres

J Med Chem. 2004 Dec 2;47(25):6270-82. doi: 10.1021/jm0493616.

Abstract

In a search for inducers of neuronal differentiation to treat neurodegenerative diseases such as Alzheimer's disease, a series of indole fatty alcohols (IFAs) were prepared. 13c (n = 18) was able to promote the differentiation of neural stem cell derived neurospheres into neurons at a concentration of 10 nM. Analysis of the expression of the Notch pathway genes in neurospheres treated during the differentiation phase with 13c (n = 18) revealed a significant decrease in the transcription of the Notch 4 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemical synthesis*
  • Alcohols / chemistry
  • Alcohols / pharmacology
  • Animals
  • Benzothiazoles
  • Cell Differentiation / drug effects
  • Fatty Alcohols / chemical synthesis*
  • Fatty Alcohols / chemistry
  • Fatty Alcohols / pharmacology
  • Free Radical Scavengers / chemical synthesis*
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Free Radicals / chemistry
  • In Vitro Techniques
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Mice
  • Neurons / cytology
  • Neurons / drug effects*
  • Oligonucleotides, Antisense / pharmacology
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Receptor, Notch1
  • Receptor, Notch2
  • Receptor, Notch4
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / genetics
  • Receptors, Notch
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology
  • Stem Cells / drug effects*
  • Structure-Activity Relationship
  • Sulfonic Acids / chemistry
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription, Genetic

Substances

  • 10-(5-methoxy-1H-indol-3-yl)decan-1-ol
  • Alcohols
  • Benzothiazoles
  • Fatty Alcohols
  • Free Radical Scavengers
  • Free Radicals
  • Indoles
  • Membrane Proteins
  • NOTCH4 protein, human
  • Notch1 protein, mouse
  • Notch2 protein, mouse
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins
  • Receptor, Notch1
  • Receptor, Notch2
  • Receptor, Notch4
  • Receptors, Cell Surface
  • Receptors, Notch
  • Sulfonic Acids
  • Transcription Factors
  • 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid