کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1391702 | 983625 | 2007 | 12 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: A Phenotypic Small-Molecule Screen Identifies an Orphan Ligand-Receptor Pair that Regulates Neural Stem Cell Differentiation A Phenotypic Small-Molecule Screen Identifies an Orphan Ligand-Receptor Pair that Regulates Neural Stem Cell Differentiation](/preview/png/1391702.png)
SummaryHigh-throughput identification of small molecules that selectively modulate molecular, cellular, or systems-level properties of the mammalian brain is a significant challenge. Here we report the chemical genetic identification of the orphan ligand phosphoserine (P-Ser) as an enhancer of neurogenesis. P-Ser inhibits neural stem cell/progenitor proliferation and self-renewal, enhances neurogenic fate commitment, and improves neuronal survival. We further demonstrate that the effects of P-Ser are mediated by the group III metabotropic glutamate receptor 4 (mGluR4). siRNA-mediated knockdown of mGluR4 abolished the effects of P-Ser and increased neurosphere proliferation, at least in part through upregulation of mTOR pathway activity. We also found that P-Ser increases neurogenesis in human embryonic stem cell-derived neural progenitors. This work highlights the tremendous potential of developing effective small-molecule drugs for use in regenerative medicine or transplantation therapy.
Journal: - Volume 14, Issue 9, 21 September 2007, Pages 1019–1030