Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Dartmouth study advances prion disease research

16.10.2003


Adding to the paradox of prion diseases, Dartmouth Medical School researchers have discovered that RNA plays a role in converting a normal prion protein into a mutant that leads to mad cow disease and other fatal brain illnesses.



Their study, reported in the Oct. 16 issue of Nature, provides important clues to understanding the role of prions, unorthodox infectious agents whose ability to transmit disease has confounded physicians and scientists. The work, by Dr. Surachai Supattapone, assistant professor of biochemistry and of medicine, opens new avenues of exploration for diagnosis and treatment of a perplexing group of neurodegenerative disorders called prion diseases.

Prions lack RNA or DNA, the nucleic acids that contain genetic information to replicate. No one knows what spurs conversion of a normal prion protein to a disease-causing counterpart. Supattapone, with coauthors Nathan Deleault and Ralf Lucassen, has discovered that RNA may be a catalyst for transformation.


"It has been well proven that nucleic acids, including RNA, are not part of the infectious agent, so it’s an ironic twist that a catalyst for the reaction may be RNA," said Supattapone. He emphasized, however, that the findings are consistent with the "protein-only" hypothesis of prion diseases because the nucleic acids are in the host and are not contained in the disease spreading particle.

Prions related to infectious brain diseases such as Cruetzfeld-Jakob disease in humans, chronic wasting or scrapie in animals have long been known, but these diseases often develop over years, so research to piece together the process has moved slowly.

The discovery more than a quarter century ago that prions were proteins, devoid of nucleic acids, upended what scientists assumed not only about disease transmission, but about life itself. All mammals have a gene to make a prion protein, but the normal prion is a different shape than the infectious prion. Somehow, this normal protein is modified into an abnormal counterpart that accumulates exponentially in the brain until death.

"It’s a curious thing, because this protein is able to stimulate its own formation and change, without nucleic acids. It’s been a fascinating question for people to come to grips with scientifically in addition to being the central reaction in an important medical problem," Supattapone said.

Now, his team has discovered that specific RNA molecules are required to transform prion proteins into their abnormal shapes. They devised a technique to observe how the normal prion protein, called PrPC, efficiently converts into the abnormal infectious protein, PrPSc (scrapie), in a test tube. This biochemical assay enabled the researchers to pinpoint the conversion mechanisms in the cell.

They found that adding enzymes that slice RNA blocked accumulation of abnormal prion protein. Taking it further, the researchers purified RNA and reconstituted the activity they had abolished with the RNA-cleaving enzymes. Adding enzyme knocked down scrapie protein and adding RNA brought it back up, indicating that RNA is really a stimulator. Moreover, RNA appears to boost the signal even of dilute amounts of scrapie protein.

The existence of RNA-converting factors could aid early detection of prion diseases, now incurable and invariably fatal. Ideal treatment time would be in the nascent stages of symptoms, before development of permanent brain damage. Current diagnosis requires a small brain biopsy, that may not provide much abnormal protein, but a technique where RNA can be added to amplify the signal may provide a more sensitive early diagnosis.

The next step is to pinpoint the RNA molecule, which seems to be only in mammals. "This stimulatory RNA appears to be a specific one, which makes it exciting to study. If we can identify, clone and produce this specific RNA, it may be useful as therapeutic target or a diagnostic tool. In addition, it may offer clues to the mechanism of conversion," Supattapone said. More studies are required to confirm the results in animals, he cautioned, but he is optimistic that the process in the test tube will contribute important insight into prion diseases.


The work was supported by the Burroughs Wellcome Fund Career Development Award, the Hitchcock Foundation and an NIH Clinical Investigator Development Award. For more information, contact Supattapone at: Surachai.Supattapone@dartmouth.edu or 603-650-1192.

Hali Wickner | EurekAlert!
Further information:
http://www.dartmouth.edu/

More articles from Studies and Analyses:

nachricht WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf

nachricht First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>