Intrinsic mechanisms of neuronal axon regeneration
Permanent disabilities following CNS injuries result from the failure of injured axons to regenerate and rebuild functional connections with their original targets. By contrast, injury to peripheral nerves is followed by robust regeneration, which can lead to recovery of sensory and motor functions. This regenerative response requires the induction of widespread transcriptional and epigenetic changes in injured neurons. Considerable progress has been made in recent years in understanding how peripheral axon injury elicits these widespread changes through the coordinated actions of transcription factors, epigenetic modifiers and, to a lesser extent, microRNAs. Although many questions remain about the interplay between these mechanisms, these new findings provide important insights into the pivotal role of coordinated gene expression and chromatin remodelling in the neuronal response to injury.
Although considerable progress has been made in understanding the mechanisms underlying peripheral nerve regeneration and how these can be manipulated to promote regeneration in the CNS, there are many challenges to overcome in order to develop therapies that achieve complete axon regrowth and functional recovery.
how injured neurons can reprogramme themselves to regrow their axons while maintaining their competency to form synapses and how they can stop growth once regeneration is complete is still not understood.
Going beyond transcriptomics to understand the use of regulatory elements, such as enhancers and promoters, and the influence of genome topology in the context of axon regeneration will also be important.
manipulating epigenetic machinery will likely be critical in efforts to improve regenerative outcomes and may need to be tailored according to age.
Common Design 