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RHO-GEF FAMILY AS DRUG TARGETS FOR AXON REGENERATION |
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Principal Investigator: A. DEBANT
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TECHNICAL DESCRIPTION
Using the screening test described below, the researchers isolated a peptide inhibitor that targets the second RhoGEF domain of the protein Trio. This inhibitor is highly specific and protects neuronal cells from serum-induced neurite retraction, indicating that this inhibitor has potential applications in axon regeneration.
The scientists used an aptamer library to determinine inhibitors of the proteins from the Rho-GEF family by a screening process that includes:
i. recovering peptide aptamers that bind to the protein of interest;
ii. recovering the peptides that specifically inhibit the in vitro exchange activity of the GEF domain of said protein;
iii. testing the capacity of the selected peptides to inhibit the activity of the RhoGEF on the appropriate GTPase in intact cells.
This RhoGEF inhibitors could have potential applications in different disease processes, such as nerve regeneration or cancer.
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