Researchers have found new protein aggregation sites that may contribute to a disabling neurodegenerative condition, Huntington’s disease. Expression of a mutant huntingtin gene creates a protein with abnormally long glutamine repeat sequences, which may cause the protein or its proteolytic fragments to aggregate in the brain. Now, Zhe-Ming Wang and Hilal A. Lashuel of the Swiss Federal Institute of Technology, Lausanne, have discovered other huntingtin sequences that may influence aggregation (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201206561). The sequences, within two coding regions of huntingtin protein, have a high tendency to aggregate and form amyloid-like fibrils. The study suggests that one or both of the sequences, if present in proteolytic huntingtin fragments, may control fragment aggregation rates and mechanisms. The researchers are currently trying to validate the tendency of these sequences to regulate not only aggregation but also potentially the proteolysis and toxicity of huntingtin fragments.