Waste management promotes regeneration

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A very surprising finding uncovers a very new way to promote functional recovery. Autophagy, the natural self-destruction of cells, seems to stabilize their “inner skeleton” and successfully promote regeneration after spinal cord injury.

What do we know so far?

After a spinal cord injury, damaged fibers cannot regenerate because of the presence of abundant inhibitory factors. Manipulating those factors promotes regeneration but in a limited way. Many of these inhibitor factors act via modulation of the cytoskeleton. The cytoskeleton is the “cellular skeleton”, which acts just like our own skeleton by giving a rigid structure. The cytoskeleton, or more precisely microtubules are not entirely stable and can “grow”, which at the cellular level corresponds to the growth of the nerve fiber.

When a neuron is damaged, many of its internal components are damaged as well. Survival and subsequently regeneration does require the total destruction of the damaged components. This highly regulated mechanism is called autophagy, and can be translated into “self-devouring” of the cell.

What are the results of the study?

First, the team found that neurons from the peripheral nervous system, which regenerates remarkably well, have an increased activity of autophagy after an injury. This led them to think that the autophagy was one of the reasons of this increased capacity to regenerate.

The first part of the study was done in vitro, meaning on neurons growing in a petri dish. Scientists were able to boost autophagy and found that this stabilized microtubules, the skeleton of the cell. This way they were even able to promote axonal growth in an “unfriendly” environment.

Then, using an experimental spinal cord injury model, that were able to increase autophagy in vivo. This was achieved by injecting a molecule called Tat-beclin1. This peptide was able to attenuate axon retraction, promoted axon regeneration and was even boosting functional recovery after injury.

What will happen next?

Further studies will have to elucidate how autophagy controls microtubules dynamics. However, this amazing discovery opens up new ways to promote recovery after an injury. A drug design based on Tat-bec has great potential for control of the cytoskeleton and axon repair.

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