Advances and Limitations of Current Epigenetic Studies Investigating Mammalian Axonal Regeneration

Axonal regeneration relies on the expression of regenerative associated genes within a coordinated transcriptional programme, which is finely tuned as a result of the activation of several regenerative signalling pathways. In mammals, this chain of events occurs in neurons following peripheral axonal injury, however it fails upon axonal injury in the central nervous system, such as in the spinal cord and the brain. Accumulating evidence has been suggesting that epigenetic control is a key factor to initiate and sustain the regenerative transcriptional response and that it might contribute to regenerative success versus failure. This review will discuss experimental evidence so far showing a role for epigenetic regulation in models of peripheral and central nervous system axonal injury. It will also propose future directions to fill key knowledge gaps and to test whether epigenetic control might indeed discriminate between regenerative success and failure. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-018-0636-1) contains supplementary material, which is available to authorized users.