Injury-Induced Decline of Intrinsic Regenerative Ability Revealed by Quantitative Proteomics

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. •Proteomics analysis of intact and injured retinal ganglion cells•Identification of a molecular network of neuronal injury responses•c-myc as a critical regulator of injury responses and axon regeneration•Functional interactions between c-myc and other known regeneration regulators Belin et al. used comparative proteomics approaches and revealed a signaling network of injury responses in axotomized retinal ganglion cells and also demonstrated c-myc as a critical regulator of neuronal survival and axon regeneration.