Because the damage from the faulty gene is limited to the corpus striatum, researchers went searching for proteins that interacted specifically and exclusively with the huntingtin protein in that part of the brain.
Rhes is found almost exclusively in the corpus striatum, according to the study.
Using human and mouse cells, researchers found that rhes interacted with both healthy and mutant versions of huntingtin protein, but that it bound much more strongly to mutant huntingtin, also known as mHtt.
"Touching or binding is one matter, but death is altogether another," Snyder said.
Further tests using human embryonic cells and brain cells taken from mice showed that when both mHtt and rhes were present in the same cells, half the cells died within 48 hours. Rhes or mHtt alone did not cause cell death.
"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," Snyder said. "And it turns out it looks like the key to Huntington's disease."
Researchers also did a set of tests to learn more about the role of rhes. Previous research has shown that the abnormal huntingtin proteins form clumps in cells throughout the body and brain, but that there are fewer of the clumps in the corpus striatum.
"This has led to much controversy: Are the clumps toxic, or is it the lack of clumps that's toxic to these brain cells?" said Srinivasa Subramaniam, a postdoctoral fellow at Johns Hopkins.
Experiments showed that adding rhes to cells with abnormal huntingtin led to fewer clumps, but the cells died.
Researchers said that the unclumping of mutant huntingtin proteins by rhes might cause the cell death.
"Since rhes is highly found in the corpus striatum, clumping somehow protects cells in other tissues of the body from dying," Subramaniam said.
The team is curr
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