Protein deiminases: new players in the developmentally regulated loss of neural regenerative ability

Dev Biol, 2011 · DOI: 10.1016/j.ydbio.2011.04.015 · Published: July 15, 2011

Spinal Cord Injury Biochemistry Regenerative Medicine & Stem Cells

Simple Explanation

The spinal cord's ability to repair itself diminishes as it develops. This study investigates why this regenerative capacity is lost. The researchers focused on enzymes called protein deiminases (PADs), specifically PAD3, and their role in this process. PADs modify proteins after they are made, which can change how they function. Blocking PAD activity with a specific inhibitor reduced cell death and tissue damage in the injured spinal cord, suggesting that PADs contribute to the loss of regenerative ability.

Study Duration

Not specified

Participants

Chick embryos

Evidence Level

Not specified

Key Findings

1
PAD3 expression increases with development and is further upregulated after spinal cord injury, particularly at stages when regeneration is less effective.
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Deimination, the process carried out by PAD enzymes, is more extensive in spinal cords that are injured at developmental stages when regeneration is poor.
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Inhibiting PAD activity reduces apoptosis and tissue loss following spinal cord injury, indicating that PADs play a role in modulating the secondary injury response.

Research Summary

This study identifies PAD3 as a developmentally-regulated enzyme expressed both in progenitors and mature neural cells that appears to be an important player in the early spinal cord injury response and in modulating its severity. The regenerative ability of the spinal cord appears to be associated with low levels and a later onset of deimination, since in E11 injured cords, unlike in E15, deimination is not detectable at two hours and is relatively low at 24 hours. Identification of this novel role for PAD activity in spinal cord injury, together with the possibility of modulating it pharmacologically with a compound that appears to display little toxicity in vivo (unlike calcium chelators), may open new avenues to reducing tissue damage in injured spinal cords.

Practical Implications

Therapeutic Target

PADs may be valuable therapeutic targets for spinal cord injury.

Early Intervention

Administering pharmacologic agents shortly after injury to reduce cellular and functional loss.

Epigenetic Role

A possible epigenetic role for histone post-translational modification in early injury response

Study Limitations

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We cannot rule out at this stage that other PADs may also play a role in the calcium-dependent secondary injury response

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