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Cellular Processes Underlying Neurodegenerative Diseases Revealed

Posted Aug 23 2012 10:09pm
Posted on Aug. 20, 2012, 6 a.m. in Cellular Reprogramming Neurology

Scientists at the University of Manchester (United Kingdom) 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 analyzing the cellular processes underlying these conditions. Andreas Prokop and colleagues 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. The team has been studying the key driver of growth cone movements, the cytoskeleton, that direct axon growth. Employing a fruit fly model to analyze how actin and microtubule proteins combine in the cytoskeleton to coordinate axon growth. They focused on the multifunctional proteins called spectraplakins which are essential for axonal growth and have known roles in neurodegeneration and wound healing of the skin. The resea4rchers discovered 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 stabilize 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 -- an important player in neurodegenerative diseases, such as Alzheimer's Disease.

Juliana Alves-Silva, Natalia Sanchez-Soriano, Robin Beaven, Melanie Klein, Jill Parkin, Andreas Prokop, et al.  “Spectraplakins Promote Microtubule-Mediated Axonal Growth by Functioning As Structural Microtubule-Associated Proteins and EB1-Dependent +TIPs (Tip Interacting Proteins).” Journal of Neuroscience, 4 July 2012, 32(27):9143-9158.

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