Effects of Indole Fatty Alcohols on the Differentiation of Neural Stem Cell Derived Neurospheres

• Published in: Journal of medicinal chemistry Vol. 47; no. 25; pp. 6270 - 6282
• Main Authors: Coowar, Djalil, Bouissac, Julien, Hanbali, Mazen, Paschaki, Marie, Mohier, Eliane, Luu, Bang
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 02.12.2004; Amer Chemical Soc
• Subjects: Alcohols - chemical synthesis; Alcohols - chemistry; Alcohols - pharmacology; Animals; Benzothiazoles; Biological and medical sciences; Cell Differentiation - drug effects; Chemistry, Medicinal; 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; Life Sciences & Biomedicine; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - physiology; Mice; Miscellaneous; Neurons - cytology; Neurons - drug effects; Neuropharmacology; Oligonucleotides, Antisense - pharmacology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; 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; Science & Technology; Stem Cells - cytology; Stem Cells - drug effects; Structure-Activity Relationship; Sulfonic Acids - chemistry; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transcription, Genetic; NEURONS; NERVOUS-SYSTEM; GENERATION; Fatty alcohol; Stem cell; Precursor cell; Nervous system; Antioxidant; Differentiation; Indole derivatives; Mechanism of action; Chemical synthesis; Radical scavenger; Biological activity; Free radical
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm0493616

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.