Advances and Limitations of Current Epigenetic Studies Investigating Mammalian Axonal Regeneration

Neurotherapeutics, 2018 · DOI: https://doi.org/10.1007/s13311-018-0636-1 · Published: June 8, 2018

Regenerative Medicine Neurology Genetics

Simple Explanation

Axonal regeneration is controlled by gene expression that is coordinated by transcriptional programs. These programs are finely tuned by the activation of regenerative signaling pathways. Epigenetic control is suggested to be a key factor in initiating and sustaining the regenerative transcriptional response, potentially determining regenerative success or failure. This review discusses experimental evidence showing the role of epigenetic regulation in axonal injury models of the peripheral and central nervous systems, proposing future research directions.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
HDAC inhibitors (HDACi) can promote neurite extension and growth cone remodeling by increasing acetylation of H3 at K9/14, requiring transcription.
2
PCAF overexpression promoted sensory axonal regeneration up to 1 mm from the lesion site in a T9-T10 spinal dorsal column crush, mimicking and surpassing the regenerative ability of a conditioning lesion.
3
Peripheral nerve injury increases TET3 and 5hmC levels in DRG, requiring calcium signaling, and TET3 knockdown abolishes nerve injury-dependent increase of 5hmC.

Research Summary

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. 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.

Practical Implications

Therapeutic Potential of Epigenetic Modulation

Targeting epigenetic mechanisms could enhance axonal regeneration after CNS injuries, such as spinal cord and brain injuries.

Personalized Medicine Approaches

Understanding neuron-specific epigenetic differences could lead to tailored therapies that maximize regenerative potential.

Drug Development for Neuroregeneration

Identifying and developing drugs that modulate specific epigenetic modifiers, like HATs and HDACs, could promote axonal regeneration.

Study Limitations

1
Heterogeneity of the nervous system poses a challenge.
2
Limited systematic comparison of transcriptional and epigenetic changes in peripheral vs central axonal injury.
3
Most studies focus on histone acetylation and methylation, neglecting other histone modifications.

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