Uncovering Neurodegenerative Diseases From Cellular Processes


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 aging.


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. By understanding the molecular detail of these interactions the team made a second important finding. Spectraplakins collect not only at the tip of microtubules but also along the shaft, which helps to stabilise them and ensure they act as a stable structure within the axon. This additional function of spectraplakins relates them to a class of microtubule-binding proteins including Tau. Tau is an important player in neurodegenerative diseases, such as Alzheimer's, which is still little understood. In support of the author's findings, another publication has just shown that the human spectraplakin, Dystonin, causes neurodegeneration when affected in its linkage to microtubules.


What Dr Prokop's paper in the Journal of Neuroscience also demonstrates is the successful research technique using the fruit fly Drosophila. The team was able to replicate its findings regarding axon growth in mice which in turn means the findings can be translated to humans. Dr Prokop points out fruit flies provide ideal means to make sense of these findings and essentially help to unravel the many mysteries of neurodegeneration.



Journal Reference:
  1. Juliana Alves-Silva, Natalia Sánchez-Soriano, Robin Beaven, Melanie Klein, Jill Parkin, Thomas H. Millard, Hugo J. Bellen, Koen J. T. Venken, Christoph Ballestrem, Richard A. Kammerer, and Andreas Prokop. Spectraplakins Promote Microtubule-Mediated Axonal Growth by Functioning As Structural Microtubule-Associated Proteins and EB1-Dependent TIPs (Tip Interacting Proteins). Journal of Neuroscience, July 4, 2012 DOI: 10.1523/%u200BJNEUROSCI.0416-12.2012