Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mystery solved: Tiny protein-activator responsible for brain cell damage in Huntington disease

08.06.2009
Johns Hopkins brain scientists have figured out why a faulty protein accumulates in cells everywhere in the bodies of people with Huntington's disease (HD), but only kills cells in the part of the brain that controls movement, causing negligible damage to tissues elsewhere.

The answer, reported this week in Science, lies in one tiny protein called "Rhes" that's found only in the part of the brain that controls movement. The findings, according to the Hopkins scientists, explain the unique pattern of brain damage in HD and its symptoms, as well as offer a strategy for new therapy.

HD itself is caused by a genetic defect that produces a mutant version of the protein "huntingtin" that gathers in all cells of the body, but only seems to affect the brain. Passed from parent to child through an alteration of a normal gene, HD over time causes irreversible uncontrolled movement, loss of intellectual function, emotional disturbances and death.

"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," says Solomon H. Snyder, M.D., professor of neuroscience at Johns Hopkins. "By finding the basic culprit, the potential is there to develop drugs that target it and either prevent symptoms or slow them down."

Curious about the huntingtin protein's striatal-specific effect, Snyder's research team, led by Srinivasa Subramaniam, Ph.D., a postdoctoral fellow, searched for proteins that interacted locally, specifically and exclusively with huntingtin in the corpus striatum, guessing that the molecular answer to the mystery most likely would be found there.

The protein Rhes caught their attention because they already were studying a related protein for other reasons. Rhes was known to be found almost exclusively in the corpus striatum.

Conducting tests using human and mouse cells, they found that Rhes interacted with both healthy and mutant versions of huntingtin protein, but bound much more strongly to mutant huntingtin, also known as mHtt.

"Touching or binding is one matter, but death is altogether another," said Snyder, so the next step was to see whether and how Rhes plus mHtt could kill brain cells in the corpus striatum.

Using human embryonic cells and brain cells taken from mice the researchers added different combinations of normal and mutant huntingtin and Rhes, and examined the cells over the next week to see if any cells died.

While each protein alone didn't change the number of cells in the dishes, when both mHtt and Rhes were present in the same cells, half the cells died within 48 hours.

"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," says Snyder. "And it turns out it looks like the key to Huntington's disease."

Snyder's team then went on to tackle another mystery surrounding the disease, the solution to this one adding further evidence for the role Rhes plays in HD.

"We've known for a long time that abnormal huntingtin proteins aggregate and form clumps in all cells of the body, but the corpus striatum of HD patients seems to have fewer of these clumps than other brain regions or the rest of the body," says Subramaniam in describing the mystery. "This has led to much controversy: Are the clumps toxic, or is it the lack of clumps that's toxic to these brain cells?"

In their experiment, adding Rhes to cells with abnormal huntingtin led to fewer clumps, but the cells died. The results, says Subramaniam, suggest that Rhes might be responsible for unclumping mutant huntingtin protein and this somehow kills cells. "Since Rhes is highly found in the corpus striatum, clumping somehow protects cells in other tissues of the body from dying," says Subramaniam.

Subramaniam and the rest of Snyder's research team currently are exploring whether removing Rhes from mice with Huntington's disease can slow or stop brain cells from dying.

"Now that we've uncovered the role of Rhes, it's possible that drugs can be designed that specifically target Rhes to treat or even prevent the disease," says Snyder.

This study was funded by a U.S. Public Health Service grant and Research Scientist Award.

Authors on the paper are Srinivasa Subramaniam, Katherine Sixt, Roxanne Barrow and Solomon H. Snyder, all of Johns Hopkins.

Audrey Huang | EurekAlert!
Further information:
http://www.jhmi.edu
http://neuroscience.jhu.edu/
http://www.sciencemag.org/

More articles from Life Sciences:

nachricht Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>