Scientists have discovered a key gene that can block brain cell death and could therefore provide a new way to halt the progress of some neurodegenerative diseases. A paper in Nature this week by Akita University researcher Junko Sasaki and colleagues explains how this Japanese team have unpicked the molecular workings of a gene called INPP4A. By knocking out the gene in mice, the researchers were able to show that it plays a crucial role in deactivating an excitatory signal called phosphatidylinositol-3,4-bisphosphate, which is produced when nerve cells are stimulated. When the INPP4A gene is absent, the team found, neurones become dangerously over-active, a state known as excitotoxicity, which ultimately kills the cell. Intriguingly, their experimental animals developed movement disorders and neurological damage very similar in nature to that seen in human patients with Huntington's disease, a relatively common and currently uncurable inherited neurodegenerative condition. The findings suggest that targeting this previously unidentified cell signalling system could therefore help to arrest the excitotoxic state that probably underlies the development of diseases like Huntington's and Parkinson's. The next step will be to look for small molecules capable of either boosting the activity of the INPP4A enzyme, or blocking the action of the phosphatidylinositol-3,4-bisphosphate signal it should be breaking down.
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