Scripps Research scientists discovered a toxic protein connected to Huntington's disease that can freely move from neurons through a nanotube tunnel constructed by a Rhes protein. The findings were published in the Journal of Cell Biology.
Dr. Srinivasa Subramaniam, a neuroscientist from the said institution, showed the reason and the process of how Huntington's disease attacks and damages specific brain cells.
"We are excited about this result because it may explain why the patient gets the disease in this area of the brain called the striatum," says Subramaniam, an associate professor in the Department of Neuroscience at Scripps Research-Florida.
Patients who inherit a damaged protein exhibit Huntington's disease. This protein that destroys brain cells was discovered in 1993 but still needs to be studied in terms of its role in this degenerative disease. Brains affected by this disease are degraded and shrunken. People affected with this disease eventually have motor control loss, memory loss, and experience emotional problems. Individuals exhibit symptoms at 30 to 40 years and could last 15 to 20 years until death. Children could also be affected with a more aggressive and rarer type of the disease that could possibly shorten their lifespan.
Most of those with Huntington's disease descend from European ancestry with 3 to 7 in 100,000 individuals affected. However, the author believes that other areas do not report cases properly.
"There is a lot of stigmas associated with the disease," says Subramaniam whose laboratory investigates the molecular mechanics of Huntington's disease and other neurodegenerative illnesses, including Alzheimer's and Parkinson's disease, to find potential therapy targets.
"In the case of Huntington's, the question is can we block this transport, and does it have any benefit or effect?" says Subramaniam.
Subramaniam and Manish Sharma experimented with the neurons of mice through a confocal microscope and they discovered that the cells aligned themselves with string-like and sticky profusions that connected cells.
"When I saw Rhes making these tunnel-like tubes between the cells I was excited and at the same time perplexed," says Sharma, the first author of the study.
"They may have been missed before because they are on a different plane," says Subramaniam. "You have to be really looking for it. It's like a bridge over a lake. If you are on the lake, you may not see the bridge above, but if you are on shore, you can see the bridge."
This tunneling nanotube in rat neurons was first described in 2004. Other scientists also discovered this phenomenon in cancer and other kinds of cells. However, details regarding how they form and what they do remain elusive to the scientific community.
The two authors tagged cells that moved through this tunnel bridge by applying it with fluorescence. They observed how the Huntington human disease protein in mouse brain cells crossed and crawled up to enter the neighboring cell. The tunnel springs back after delivery of its shipment.
The Rhes protein exists in both mouse and human brains sick with Huntington's disease. Knocking out the Rhes gene in diseased mice results in less brain damage. In the 2009 study, Subramaniam found that Rhes also alters the Huntington disease protein's structure making it more toxic to brain cells.
"The Rhes protein makes its own road. That is what is surprising to us," says Subramaniam. "But it not only transports itself. Once the road is made, many things can be transported."
