Research opens avenues in combating neurodegenerative diseases

Scientists at the University of Manchester have uncovered how the internal mechanisms in nerve cells wire the brain. The findings open up new avenues in the investigation of neurodegenerative diseases by analysing the cellular processes underlying these conditions.

Illustration of spectraplakins in axonal growth organising microtubules

Dr Andreas Prokop and his team at the faculty of life sciences have been studying the growth of axons, the thin cable-like extensions of nerve cells that wire the brain. If axons don't develop properly this can lead to birth disorders, mental and physical impairments and the gradual decay of brain capacity during ageing.

Axon growth is directed by the hand shaped growth cone which sits in the tip of the axon. It is well documented how growth cones perceive signals from the outside to follow pathways to specific targets, but very little is known about the internal machinery that dictates their behaviour.

Dr Prokop has been studying the key driver of growth cone movements, the cytoskeleton. The cytoskeleton helps to maintain a cell's shape and is made up of the protein filaments, actin and microtubules. Microtubules are the key driving force of axon growth whilst actin helps to regulate the direction the axon grows.

Dr Prokop and his team used fruit flies to analyse how actin and microtubule proteins combine in the cytoskeleton to coordinate axon growth. They focussed on the multifunctional proteins called spectraplakins which are essential for axonal growth and have known roles in neurodegeneration and wound healing of the skin.

What the team demonstrate in this recent paper is that spectraplakins link microtubules to actin to help them extend in the direction the axon is growing. If this link is missing then microtubule networks show disorganised criss-crossed arrangements instead of parallel bundles and axon growth is hampered.