oxalylglycine and Peripheral-Nerve-Injuries

Despite the ability of peripheral nerves to regenerate after injury, failure occurs due to an inability of supporting cells to maintain growth, resulting in long-term consequences such as sensorimotor dysfunction and neuropathic pain. Here, we investigate the potential of engaging the cellular adaptive response to hypoxia, via inhibiting its negative regulators, to enhance the regenerative process. Under normoxic conditions, prolyl hydroxylase domain (PHD) proteins 1, 2, and 3 hydroxylate the key metabolic regulator hypoxia inducible factor 1α (HIF1α), marking it for subsequent proteasomal degradation. We inhibited PHD protein function systemically via either individual genetic deletion or pharmacological pan-PHD inhibition using dimethyloxalylglycine (DMOG). We show enhanced axonal regeneration after sciatic nerve crush injury in PHD1

Topics: Amino Acids, Dicarboxylic; Animals; Axons; Cells, Cultured; Hypoxia; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Regeneration; Peripheral Nerve Injuries; Prolyl Hydroxylases; Prolyl-Hydroxylase Inhibitors; Recovery of Function