Discovery of a Small Molecule that Enhances Astrocytogenesis by Activation of STAT3, SMAD1/5/8, and ERK1/2 via Induction of Cytokines in Neural Stem Cells

作者：Lee Ha Rim; Farhanullah; Lee JiSoo; Jajoo Rahul; Kong Sun Young; Shin Jae Yeon; Kim Jae Ouk; Lee Jiyoun; Lee Jeewoo; Kim Hyun Jung^*

来源：ACS Chemical Neuroscience, 2016, 7(1): 90-99.

DOI：10.1021/acs.chemneuro.5b00243

• Astrocytogenesis
• neural stem cells
• neurological agents
• structure-activity relationships
• neurodegeneration
• differentiation

Identification of small molecules that direct neural stem cells (NSCs) into specific cell types would be helpful to understand the molecular mechanisms involved in regulation of NSC fate, and facilitate the development of therapeutic applications. In the current study, we developed and screened small molecules that can modulate the fate of NSCs that are derived from rat fetal cortex. Among these compounds, compounds 5 and 6 successfully differentiated NSCs into astrocytes and neurons, respectively. Compound 5 induced astrocytogenesis by increasing expression of interleukin-6, bone morphogenetic protein 2 and leukemia inhibitory factor and through consequent phosphorylation of signal transducer and activator of transcription 3 and Sma- and Mad-related protein 1/5/8 in NSCs. In addition, compound 5 increased the expression of fibroblast growth factor (FGF) 2 and FGF8 which may regulate the branching and morphology of astrocytes. Taken together, our results suggest that these small molecules can serve as a useful tool to study cell fate determination in NSCs and be used as an inexpensive alternative to cytokines to study mechanisms of astrocytogenesis.

• 出版日期2016-1