Injury-induced decline of intrinsic regenerative ability revealed by quantitative proteomics

Neuron. 2015 May 20;86(4):1000-1014. doi: 10.1016/j.neuron.2015.03.060. Epub 2015 Apr 30.


Neurons differ in their responses to injury, but the underlying mechanisms remain poorly understood. Using quantitative proteomics, we characterized the injury-triggered response from purified intact and axotomized retinal ganglion cells (RGCs). Subsequent informatics analyses revealed a network of injury-response signaling hubs. In addition to confirming known players, such as mTOR, this also identified new candidates, such as c-myc, NFκB, and Huntingtin. Similar to mTOR, c-myc has been implicated as a key regulator of anabolic metabolism and is downregulated by axotomy. Forced expression of c-myc in RGCs, either before or after injury, promotes dramatic RGC survival and axon regeneration after optic nerve injury. Finally, in contrast to RGCs, neither c-myc nor mTOR was downregulated in injured peripheral sensory neurons. Our studies suggest that c-myc and other injury-responsive pathways are critical to the intrinsic regenerative mechanisms and might represent a novel target for developing neural repair strategies in adults.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Axons / pathology
  • Axotomy / methods
  • Cell Survival / physiology
  • Disease Models, Animal
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Regeneration / physiology*
  • Neurons / metabolism
  • Neurons / pathology
  • Optic Nerve / metabolism
  • Optic Nerve / pathology
  • Optic Nerve Injuries / metabolism*
  • Proteomics*
  • Retinal Ganglion Cells / metabolism*
  • Signal Transduction / physiology