Title of article :
A Phenotypic Small-Molecule Screen Identifies an Orphan Ligand-Receptor Pair that Regulates Neural Stem Cell Differentiation Original Research Article
Author/Authors :
Jonathan P. Saxe، نويسنده , , Hao Wu، نويسنده , , Theresa K. Kelly، نويسنده , , Michael E. Phelps، نويسنده , , Yi E. Sun، نويسنده , , Harley I. Kornblum، نويسنده , , Jing Huang، نويسنده ,
Issue Information :
ماهنامه با شماره پیاپی سال 2007
Pages :
12
From page :
1019
To page :
1030
Abstract :
High-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 title :
Chemistry and Biology
Serial Year :
2007
Journal title :
Chemistry and Biology
Record number :
1159425
Link To Document :
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