Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Variant prion protein causes infection but no symptoms

03.06.2005


Finding could have implications for Alzheimer’s disease


Abnormal prion proteins (red stain) also appear as plaques (green stain) in the brains of scrapie-infected mice expressing anchorless prion proteins.



Abnormal prion proteins are little understood disease agents involved in causing horrific brain-wasting diseases such as Creutzfeldt-Jacob disease in people, mad cow disease in cattle and chronic wasting disease in deer and elk. Now, new research suggests that a variant form of abnormal prion protein--one lacking an "anchor" into the cell membrane--may be unable to signal cells to start the lethal disease process, according to scientists at the Rocky Mountain Laboratories (RML), part of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health.

"This work provides novel insights into how prion and other neurodegenerative diseases develop and it provides tantalizing clues as to how we might delay or even prevent such diseases by preventing certain cellular interactions," notes NIAID Director Anthony S. Fauci, M.D. A paper describing the research was released online today by the journal Science. RML virologist Bruce Chesebro, M.D., directed the project. Other key co-authors from the Hamilton, MT, RML laboratory include Richard Race, D.V.M., and Gerald Baron, Ph.D. Their collaborators included Michael Oldstone, M.D., and Matthew Trifilo, Ph.D., of The Scripps Research Institute in La Jolla, CA, and Eliezer Masliah, M.D., of the University of California, San Diego (UCSD).


Drawing on experimental concepts first developed at RML a decade ago, the research team exposed two groups of 6-week-old mice to different strains of the agent that causes scrapie, a brain-wasting disease of sheep. Within 150 days of being inoculated with the natural form of scrapie prion protein, all 70 mice in the control group showed visible signs of infection: twitching, emaciation and poor coordination. In contrast, the scientists observed 128 transgenic mice--those engineered to produce prion protein without a glycophosphoinositol (GPI) cell membrane anchor--for 500 to 600 days and saw no signs of scrapie disease. Subsequent electron microscopic examinations at UCSD, however, confirmed that they produced amyloid fibrils, an abnormal form of prion protein, and that they even had brain lesions. More remarkably, according to Dr. Chesebro, the diseased brain tissue resembled that found in Alzheimer’s disease rather than in scrapie.

Chesebro mentions two theories as to why the transgenic mice did not show symptoms of illness despite being infected:

  • The host cell might require the GPI anchor to receive the "toxic signal" from the abnormal prion protein
  • The plaques might be less toxic than the non-plaque form of prion protein clumps

In either case, more time might be required to produce disease due to the reduced toxicity, Dr. Chesebro says.

"There was so much about this research that surprised us and gave us ideas to pursue," says Dr. Chesebro. "First, the mice didn’t get sick. That’s very significant. Second, the dense accumulations of scrapie plaque in the brain resembled the plaque seen in Alzheimer’s, but it wasn’t toxic," which might support more recent concepts about plaque in Alzheimer’s patients. "Previously, most researchers thought plaques were the toxic component of Alzheimer’s that kills neurons, and many treatments focus on removing the plaques. But what if the plaques are inert, as they were in this research? What if only small clumps are toxic?"

If this hypothesis proves correct, Dr. Chesebro says, the ongoing research could eventually alter scientists’ views on preventing prion diseases, shifting emphasis away from stopping the production of prion protein clumps and toward preventing interactions with prion protein anchored to cells, or learning to direct abnormal prion protein accumulations to specific parts of the brain where they will not produce symptoms.

"Abnormal prion protein by itself may not be rapidly lethal--in these mice it wasn’t," Dr. Chesebro says.

Ken Pekoc | EurekAlert!
Further information:
http://www.niaid.nih.gov

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>