Poly(ADP-ribose) polymerase 1 is a novel target to promote axonal regeneration Academic Article uri icon

Overview

MeSH Major

  • Axons
  • Enzyme Inhibitors
  • Nerve Regeneration
  • Poly(ADP-ribose) Polymerases

abstract

  • Therapeutic options for the restoration of neurological functions after acute axonal injury are severely limited. In addition to limiting neuronal loss, effective treatments face the challenge of restoring axonal growth within an injury environment where inhibitory molecules from damaged myelin and activated astrocytes act as molecular and physical barriers. Overcoming these barriers to permit axon growth is critical for the development of any repair strategy in the central nervous system. Here, we identify poly(ADP-ribose) polymerase 1 (PARP1) as a previously unidentified and critical mediator of multiple growth-inhibitory signals. We show that exposure of neurons to growth-limiting molecules-such as myelin-derived Nogo and myelin-associated glycoprotein-or reactive astrocyte-produced chondroitin sulfate proteoglycans activates PARP1, resulting in the accumulation of poly(ADP-ribose) in the cell body and axon and limited axonal growth. Accordingly, we find that pharmacological inhibition or genetic loss of PARP1 markedly facilitates axon regeneration over nonpermissive substrates. Together, our findings provide critical insights into the molecular mechanisms of axon growth inhibition and identify PARP1 as an effective target to promote axon regeneration.

publication date

  • December 8, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4679058

Digital Object Identifier (DOI)

  • 10.1073/pnas.1509754112

PubMed ID

  • 26598704

Additional Document Info

start page

  • 15220

end page

  • 5

volume

  • 112

number

  • 49