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

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.

Regulation of a Notch3-Hes1 Pathway and Protective Effect by a Tocopherol-Omega Alkanol Chain Derivative in Muscle Atrophy

“…Indeed, AGT251 treatment partly counteracted both in vitro and in vivo stress-induced Notch pathway activation. However, in C2C12 myoblastic cells and in muscles of ALS or doxorubicin-treated animals, the repression was mostly observed on Notch1 and Notch3 but not on Notch4 as previously seen in neurons (Coowar et al, 2004). In addition, here we also provided the first evidence that regulation of the Notch receptor by tocopherol derivatives impacts the Notch target genes.…”

“…shown that tocopherol derivatives repressed mRNA level for Notch4 in neuronal cells (Coowar et al, 2004). Our study brings novel information on these two aspects.…”

“…At the dose of AGT251 that favored survival (10 mM), the cisplatin-induced expression of p21 was To further understand the biologic properties of the AGT251 tocopherol derivative, we then focused on the Notch pathway for two reasons. First, previous work has shown that compounds sharing a similar structure to our compounds were able to repress Notch4 RNA expression in neurospheres correlating with an increased neuronal survival (Coowar et al, 2004;Blanchard et al, 2013). Second, it has been shown that the notch pathway plays a key role in muscle regeneration and myoblast survival (Buas and Kadesch, 2010;Bjornson et al, 2012) and is regulated by the physiologic status of the mitochondria (Arthur and Cooley, 2012; Kasahara et al, 2013).…”

“…Several molecules that act on regeneration and neuroprotection are derived from tocopherol, a member of the vitamin E family, which is widely used in clinical practice because of its antioxidant and anti-inflammatory properties (Singh and Jialal, 2004). Moreover, a-tocopherol derivatives are considered disease modulators in multiple sclerosis and show beneficial outcomes after white matter damage in experimental models (Coowar et al, 2004;Blanchard et al, 2013).…”

Synthesis, Fluorescence Properties and Biological Activity of 8‐Hydroxyquinoline Conjugate Bonded Aromatic Heterocyclic Derivatives

“…9 Several small heterocyclic molecules have been demonstrated to be capable of inducing stem-cell proliferation and differentiation in vitro. 10,11 8-Hydroxyquinoline derivatives are important constituents in a variety of pharmaceutically important compound classes. They have become of interest as a new class of potent HIV-1 integrase inhibitors, 12 for modeling of the inhibition of retroviral integrases, 13 as protein tyrosine kinase inhibitors, 14 as protozoal and retroviral co-infections 15 and as anti-HIV-1 agents.…”