Cracking the code of Huntington's disease

Huntington's disease is caused by a gene mutation that causes a protein to build up in the brain. In a world first, EPFL scientists have synthesized and studied modified forms of a mutant part of the protein, deepening our understanding of how it contributes to the disease, and pointing to new therapeutic strategies for treating it. Huntington's disease is a neurodegenerative disorder that causes patients to lose their ability to move, speak, and even think. It is caused by a gene mutation that produces an abnormal form of the protein huntingtin, which aggregates and builds up inside neurons of the cortex and striatum. Small chemical modifications on different parts of huntingtin could reduce its toxicity and aggregation, but as many enzymes already chemically modify the protein in the cell, it has been difficult to determine what chemical modifications could serve as future therapies. EPFL scientists have now developed synthetic methods that allow site-specific chemical modifications on huntingtin while bypassing the need to identify the enzymes behind them. The study is published in Angewandte Chemie . After being produced by its gene, huntingtin is subjected to numerous chemical changes, during which enzymes in the cell attach different chemical groups to it, such as phosphate (phosphorylation) or acetylene (acetylation).