ADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS

Neuron, 2019 · DOI: 10.1016/j.neuron.2019.07.007 · Published: September 25, 2019

Regenerative Medicine Neurology Genetics

Simple Explanation

Injured nerve fibers in the brain and spinal cord don't regrow well, limiting recovery from injuries and diseases. This study found that a protein called ADF/Cofilin, which helps cells change shape during development, can be reactivated to promote nerve fiber regeneration after spinal cord injury. ADF/Cofilin works by increasing the turnover of actin, a protein that forms the cell's skeleton. This increased turnover helps the nerve fiber's growth cone (the tip of the growing fiber) to move and extend. Activating ADF/Cofilin alone can trigger nerve fiber regeneration, suggesting it's a key control point. This finding could lead to new therapies that promote nerve repair after CNS injuries.

Study Duration

Not specified

Participants

Adult Sprague Dawley rats, wild type (WT, C57BL/6J) and transgenic mice

Evidence Level

Not specified

Key Findings

1
Elevated actin turnover is essential for regenerative growth of axons following a conditioning lesion.
2
ADF/Cofilin activity is increased during conditioning-mediated axon regeneration.
3
ADF/Cofilin is both necessary and sufficient for axon regeneration in the adult CNS.

Research Summary

The study identifies ADF/Cofilin-mediated actin turnover as a molecular mechanism to induce axon regeneration, mimicking processes during development. Conditioning increases actin dynamics by enhancing the actin-severing activity of AC, which is required for axon regeneration. Overexpression of Cofilin1 without prior conditioning was sufficient to induce regeneration, both in cell culture and in vivo after spinal cord injury.

Practical Implications

Therapeutic Target

ADF/Cofilin-mediated actin turnover can be a promising therapeutic target for regenerative therapies after CNS injuries.

Drug Development

Actin-manipulating drugs, including cytochalasins and latrunculins, could stimulate axon regeneration.

Plasticity Potential

Adult CNS neurons retain the capacity to activate developmental programs for plasticity and regeneration.

Study Limitations

1
The genetic analysis was challenged by the expression of a third member of the AC family in the adult nervous system, Cofilin2, which can compensate for the loss of ADF and Cofilin1.
2
The exact biochemical differences among the isoforms are still controversial.
3
Future pharmacological actin manipulations need to be well-adjusted so that non-neuronal cells at the lesion site are able to preserve their essential actin-based elements, including tight junctions.

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