Scientists at Johns Hopkins have shown evidence that a novel protein (Rhes) located chiefly in a key area of the brain (the corpus striatum), may be a clue to the mystery of why abnormal huntintin protein, although present in cells throughout the body, exerts its cell-killing and disease-causing effects primarily in the corpus striatum. The findings, according to the Hopkins scientists, explain the unique pattern of brain damage in Huntingtin disease (HD) and its symptoms, as well as offer a strategy for new therapy. “It's always been a mystery why, if the protein made by the HD gene is seen in all cells of the body, only the brain, and only a particular part of the brain, the corpus striatum, deteriorates," said Dr. Solomon H. Snyder, senior author of the report. "By finding the basic culprit (Rhes), the potential is there to develop drugs that target it and either prevent symptoms or slow them down." In their work, the researchers showed that the Rhes protein interacts with the huntingtin protein, but much more strongly with the mutant, disease-causing version than with the normal version. They further showed that presence of both the Rhes protein and the huntingtin protein in cells led to speedy cell death, while the presence of either protein alone did not. They also observed that the presence of the Rhes protein resulted in less clumping of the huntingtin protein in cells, than did the absence of Rhes protein. This could be an explanation for why, in HD, less clumping of huntingtin is observed in the corpus striatum than in the unaffected cells in the body, even though clumping has been proposed, by some, as a cause of the disease. "Here's the Rhes protein, we've known about it for years, nobody ever really knew what it did in the brain or anywhere else," said Dr. Snyder.
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