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 Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

nachricht Scientists reveal source of human heartbeat in 3-D
07.08.2017 | University of Manchester

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>