Potent Modulators of GPR126 Promote Schwann Cell-Mediated Myelination of Peripheral Nerve Axons

  • Discovering potent GPR126 modulators, including picomolar peptide agonists and low-molecular-weight agonists/PAMs, and using cryo-EM to reveal a novel allosteric binding site
  • Demonstrating that agonist and PAM modulation of GPR126 increases axon myelination in a Schwann cell in vitro model via activation of myelination pathways
  • Presenting aGPCRs as tractable drug targets, with GPR126 modulation offering a promising route for developing therapeutics for peripheral neuropathies