More Good News in the fight against HD March 27, 2001 There is more exciting news this week in the fight against Huntington disease. On 23 March, Dr. Christopher Ross of Johns Hopkins University School of Medicine, and colleagues at Niigata University in Japan announced in the prestigious journal Science that they have discovered a possible explanation for the death of brain cells in Huntington disease. Dr. Ross has found that a protein which is important to the survival of cells is kidnapped by the defective protein produced by the Huntington disease gene. The Huntington=s gene produces a protein (huntingtin) which contains too many units of a particular kind of amino acid, called glutamine. This polyglutamine expansion, it has been suggested, prevents the huntingtin protein from behaving normally and causes interactions between huntingtin and other proteins within brain cells, which lead eventually to cell death. The huntingtin protein is known to form aggregates, or protein balls, and the role of these protein balls in cell death has been a key question in HD research. Now, Dr. Ross has demonstrated that the role of protein balls may be that they Amake off with@ other proteins which are needed for cells to survive. More specifically, Dr. Ross and his colleagues focused on a particular protein called CBP (CREB binding protein), which plays an important role in cell survival and which contains a short length of the glutamines which are so dramatically expanded in Huntington disease. Using cell models, the researchers demonstrated that CBP is kidnapped by huntingtin protein, drawn into protein aggregates and away from its normal location within the cell. This prevents CBP from performing its critical function in promoting cell survival. These findings were mirrored in a mouse model of HD and in postmortem tissue from humans with HD. The most exciting news is Dr. Ross= discovery that, in a cell model, dramatically boosting the expression of CBP rescued cells from death. These findings represent another dramatic breakthrough in our understanding of the causes of cell death in Huntington disease C it would appear that it is not protein aggregates themselves which cause cell death, but rather their interactions with CBP and, quite likely, with other proteins in brain cells. Most importantly, Dr. Ross indicates that Athese interactions might be targets for future therapeutics. Disponible en français.