Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Brown Team Finds Crucial Protein Role in Deadly Prion Spread

25.01.2007
Brown University biologists have made another major advance toward understanding the deadly work of prions, the culprits behind fatal brain diseases such as mad cow and their human counterparts. In new work published online in PLoS Biology, researchers show that the protein Hsp104 must be present and active for prions to multiply and cause disease.

A single protein plays a major role in deadly prion diseases by smashing up clusters of these infectious proteins, creating the “seeds” that allow fatal brain illnesses to quickly spread, new Brown University research shows.

The findings are exciting, researchers say, because they might reveal a way to control the spread of prions through drug intervention. If a drug could be made that inhibits this fragmentation process, it could substantially slow the spread of prions, which cause mad cow disease and scrapie in animals and, in rare cases, Creutzfeldt-Jacob disease and kuru in humans.

Because similar protein replication occurs in Alzheimer’s and Parkinson’s diseases, such a drug could also slow progression of these diseases as well.

... more about:
»Hsp104 »Serio »fragmentation »multiply

“The protein fragmentation we studied has a big impact on how fast prion diseases spread and may also play a role in the accumulation of toxic proteins in neurodegenerative diseases like Parkinson’s,” said Tricia Serio, an assistant professor in Brown’s Department of Molecular Biology, Cell Biology and Biochemistry and lead researcher on the project.

The findings from Serio and her team, which appear online in PLoS Biology, build on their groundbreaking work published in Nature in 2005. That research showed that prions – strange, self-replicating proteins that cause fatal brain diseases – convert healthy protein into abnormal protein through an ultrafast process.

This good-gone-bad conversion is one way that prions multiply and spread disease. But scientists believe that there is another crucial step in this propagation process – fragmentation of existing prion complexes. Once converted, the thinking goes, clusters of “bad” or infectious protein are smashed into smaller bits, a process that creates “seeds” so that prions multiply more quickly in the body. Hsp104, a molecule known to be required for prion replication, could function as this protein “crusher,” Serio thought.

To test these ideas, Serio and members of her lab studied Sup35, a yeast protein similar to the human prion protein PrP. They put Sup35 together with Hsp104, then activated and deactivated Hsp104. They found that the protein does, indeed, chop up Sup35 complexes – the first direct evidence that this process occurs in a living cell and that Hsp104 is the culprit.

“To understand how fragmentation speeds the spread of prions, think of a dandelion,” Serio said. “A dandelion head is a cluster of flowers that each carries a seed. When the flower dries up and the wind blows, the seeds disperse. Prion protein works the same way. Hsp104 acts like the wind, blowing apart the flower and spreading the seeds.”

Serio said that prions still multiply without fragmentation. However, she said, they do so at a much slower rate. So a drug that blocked the activity of Hsp104 could seriously slow progression of prion-related diseases.

Former graduate student Prasanna Satpute-Krishnan and research associate Sara Langseth, also in Brown’s Department of Molecular Biology, Cell Biology and Biochemistry, conducted the work with Serio.

The National Cancer Institute, the National Institute of General Medical Sciences, and the Pew Scholars Program in the Biomedical Sciences funded the research.

Editors: Brown University has a fiber link television studio available for domestic and international live and taped interviews and maintains an ISDN line for radio interviews. For more information, call the Office of Media Relations at (401) 863-2476.

Wendy Lawton | Brown University
Further information:
http://www.brown.edu

Further reports about: Hsp104 Serio fragmentation multiply

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

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

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>