TUESDAY, March 7, 2006 (HealthDay News) -- Experts have long thought that clumps of misfolded proteins in the brains of Huntington's disease patients were a sign or cause of damage.
However, new research suggests they might actually help the brain defend itself against the debilitating illness.
A compound that boosted the formation of these "inclusions," as the clumps are called, also revved up a molecular mechanism that rids cells of abnormal proteins.
What's more, laboratory tests that focused on Parkinson's disease -- where abnormal clumping also occurs -- got the same results.
Researchers believe the finding might open a new approach to treating both of these devastating neurodegenerative conditions, said lead researcher Ruth A. Bodner, a postdoctoral fellow at the Massachusetts Institute of Technology.
Her team published its findings in this week's early online edition of Proceedings of the National Academy of Sciences.
Inclusions found in both Huntington's and Parkinson's are clearly capable of doing damage, Bodner stressed. "But, there are different conformations that the proteins can take," she added. "They can be soluble [and] they can be in the form of large inclusions, and there is increasing evidence that the large inclusions might be protective."
Just how clumped proteins help shield brain cells remains unclear. According to Bodner, it could be that having these abnormal proteins arranged in a clump hems in their toxicity. At any rate, a protein identified through a simple screening test and called B2 increased clumping and boosted the functioning of proteasomes -- molecular systems that rid the cells of bad proteins.
The search for effective treatments for Huntington's disease has typically focused on ways to prevent inclusions from forming, Bodner said. But now, "we think there is room for a different approach," she said.
Dr. Steve Finkbeiner, assistant investigator at the University of California, San Francisco's Gladstone Institute of Neurological Disease, said the MIT work supports earlier findings from his lab.
"In 2004 we used a robotic microscope to show that inclusion formation predicted better survival in Huntington's disease," Finkbeiner said. "This is substantiation of that idea."
Finkbeiner and his colleagues theorize that the potentially toxic abnormal proteins exist in multiple forms, and that the damage is done by individual proteins or very small collections of them. The idea about inclusions is that "they effectively mothball the more toxic forms," Finkbeiner said.
But if a new treatment for Huntington's and Parkinson's diseases is to come from the MIT work, it is still a long way off, Bodner said. Work at MIT remains at the basic science level, she said.
"We'd like to find a more powerful analogue [form] of B2," Bodner said. "If we could, it might direct us to new targets as well."
The researchers are trying to get even more basic information about the B2 protein. Right now, "we don't know what it is interacting with," Bodner pointed out. "Our work with Parkinson's disease makes us think it is involved with protein target control."
More information
To learn more about Huntington's disease, visit the Huntington's Disease Society of America.
