Soluble adenylyl cyclase is necessary and sufficient to overcome the block of axonal growth by myelin-associated factors. Academic Article uri icon

Overview

abstract

  • Neurons in the CNS do not regenerate following injury; regeneration is blocked by inhibitory proteins in myelin, such as myelin-associated glycoprotein (MAG). Elevating neuronal levels of the second messenger cAMP overcomes this blocked axonal outgrowth. One way to elevate cAMP is pretreating neurons with neurotrophins, such as brain-derived neurotrophic factor (BDNF). However, pleiotropic effects and poor bioavailability make exogenous administration of neurotrophins in vivo problematic; therefore, alternative targets must be considered. In neurons, two families of adenylyl cyclases synthesize cAMP, transmembrane adenylyl cyclases (tmACs), and soluble adenylyl cyclase (sAC). Here, we demonstrate that sAC is the essential source of cAMP for BDNF to overcome MAG-dependent inhibition of neurite outgrowth. Elevating sAC in rat and mouse neurons is sufficient to induce neurite outgrowth on myelin in vitro and promotes regeneration in vivo. These results suggest that stimulators of sAC might represent a novel therapeutic strategy to promote axonal growth and regeneration.

publication date

  • July 9, 2014

Research

keywords

  • Adenylyl Cyclases
  • Axons
  • Cerebellum
  • Myelin Proteins
  • Nerve Regeneration

Identity

PubMed Central ID

  • PMC4087207

Scopus Document Identifier

  • 84904011380

Digital Object Identifier (DOI)

  • 10.1074/jbc.M113.510073

PubMed ID

  • 25009261

Additional Document Info

volume

  • 34

issue

  • 28