Acetylation as a mechanism that regulates axonal regeneration.

Abstract

The capacity for adult axons to regenerate after injury is diminished compared with developing axons. In the case of central nervous system (CNS) axons, injury causes a total failure to regenerate. This failure is due to both the intrinsic developmental decrease in growth capacity and the extrinsic inhibitory environment formed because of the injury. One way to re-invigorate mature axons into a regrowth state is to induce regenerative gene expression in the nucleus to increase the intrinsic growth state of the neuron. One potential mechanism is through changes in epigenetic factors. Another possible method is to alter posttranslational modifications in axonal and growth cone microtubules of the axonal cytoplasm (Trakhtenberg and Goldberg, 2012; Cho and Cavalli, 2014). An increasing number of studies have turned to epigenetic manipulation using pharmacological inhibitors to try and enhance axonal growth. Numerous reversible posttranslational modifications are considered important for axonal growth and regeneration but such modifications are regulated by families of enzymes which affect system wide changes in the body, sometimes shuttling between the nucleus and the cytoplasm as well as between the cell body and axon. Two families of enzymes, histone acetyl transferases (HATs) and histone deacetylases (HDACs), act antagonistically to affect acetylation and de-acetylation respectively on many proteins throughout the body. Acetylation in neurons is critical for many physiological events such as cell division, cell growth and proliferation. This paper will focus on the potential implications of acetylation homeostasis on axonal growth.