PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure.

ABSTRACT: The molecular mechanisms discriminating between regenerative failure and success remain elusive. While a regeneration-competent peripheral nerve injury mounts a regenerative gene expression response in bipolar dorsal root ganglia (DRG) sensory neurons, a regeneration-incompetent central spinal cord injury does not. This dichotomic response offers a unique opportunity to investigate the fundamental biological mechanisms underpinning regenerative ability. Following a pharmacological screen with small-molecule inhibitors targeting key epigenetic enzymes in DRG neurons, we identified HDAC3 signalling as a novel candidate brake to axonal regenerative growth. In vivo, we determined that only a regenerative peripheral but not a central spinal injury induces an increase in calcium, which activates

SUBMITTER: Hervera A 

PROVIDER: S-EPMC6600644 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature