James Fawcett, University of Cambridge, Centre for Brain Repair , Cambridge, United Kingdom

A novel regeneration scaffolding molecule

Funded in: 2019, 2020, 2021


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Problem: No effective treatment for long distance nerve fibre regeneration

Target: Protrudin can restore much of the regeneration ability to mature neurons

Goal: Find the best combination of molecules to restore regeneration to the corticospinal tract

 

Long distance nerve fibre regeneration is the most important requirement for spinal cord repair, but there is currently no sufficiently effective treatment to achieve it. Neurons during embryonic growth are powerful regenerators, but as they mature their ability to regenerate nerve fibres is lost. The research group has identified a new and powerful stimulator called protrudin which can restore much of the regeneration ability to mature neurons. Protrudin comes from a class of molecule known as a scaffolder, which gather together a tool kit of molecules in a particular place to perform a function. Protrudin brings together many of the key molecules that are needed for nerve fibre regeneration. In particular it brings together cell surface adhesion and receptor molecules needed for growth, molecules needed to make the cytoskeleton dynamic and the endoplasmic reticulum (an organelle that participates in membrane production and signalling). In the laboratory the research group has produced a form of protrudin that is always in the activated state and they have found that it has a very powerful stimulating effect on regeneration. A pilot experiment on regeneration in the optic nerve showed profuse regeneration over a long distance. In this Wings for Life project they will test protrudin for its ability to enhance regeneration of corticspinal motor fibres in the spinal cord. The researchers will combine it with some other stimulators of regeneration to provide cell surface receptor integrins and other molecules that enable growth molecules to be transported to the cut end of damaged nerve fibres. The aim is to find the best combination of molecules to restore regeneration to the motor fibres of the corticospinal tract.