Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Prion discovery could help keep deadly brain diseases in check

17.01.2014
New research from David Westaway, PhD, of the University of Alberta and Jiri Safar, PhD, Case Western Reserve University School of Medicine has uncovered a quality control mechanism in brain cells that may help keep deadly neurological diseases in check for months or years.

The findings, published in The Journal of Clinical Investigation, "present a breakthrough in understanding the secret life of prion molecules in the brain and may offer a new way to treat prion diseases," said Westaway, Director of the Centre for Prions and Protein Folding Diseases and Professor of Neurology in the Faculty of Medicine and Dentistry at the University of Alberta.

Prion diseases lead to incurable neurodegenerative disorders such as Creutzfeldt-Jakob disease in humans, mad cow disease (Bovine Spongiform Encephalopathy) and chronic wasting disease in deer and elk. The diseases are caused by the conversion of normal cellular prion proteins into the diseased form.

For years, scientists have been perplexed by two unexplained characteristics of prion infections: vastly differing asymptomatic periods lasting up to five decades and when symptoms do arise, greatly varying accumulation of the diseased proteins. In striking contrast, test tube prions replicate rapidly, and in a matter of days reach levels found in brains in the final stage of the disease.

"Our study investigated the molecular mechanism of this intriguing puzzle," said Safar, Co-Director of the National Prion Disease Pathology Surveillance Center and Associate Professor in Departments of Pathology and Neurology in Case Western Reserve University School of Medicine.

In probing these mysteries, Westaway, Safar, their teams and other collaborating researchers in the U.S., Italy and the Netherlands studied a molecule called the 'shadow of the prion protein.'

"Dramatic changes in this shadow protein led us to expand our view to include the normal prion protein itself," said Westaway. "This is a crucial molecule in brain cells because it is pirated as the raw material to make diseased prion proteins."

The production and degradation of the normal prion protein had previously received little attention because it was assumed its production pipeline did not vary.

"The puzzle of the long asymptomatic time period required sorting out the different types of prion protein molecules. Our laboratory developed new techniques to tease out these subtle differences in shape," Safar said.

The researchers discovered a marked drop in the amount of the normal prion protein in eight different types of prion diseases. Strikingly, this drop occurred months or years before the animal models showed tell-tale clinical symptoms of the brain disease.

"Our belief is that cells under prion attack are smarter than we once thought," Westaway said. "They not only sense the molecular piracy by the diseased proteins, but they also adopt a simple and at least partly effective protective response – they minimize the amount raw material from the pipeline for prion production."

"We believe we can kill two birds with one stone, because the normal prion protein is also a receptor for toxicity. Augmenting this natural protective response may be a preferred route to cure prion infections," Safar added.

The study's discovery of a natural protective response can also explain the long latency period in other more common neurodegenerative diseases.

"The pre-clinical phase of the disease—before it shows symptoms—is when you want to set things straight. We may be able to take a slow disease and bring it to a complete standstill," Westaway said. "Since some scientists believe the normal prion protein is an accessory in the brain cell death of Alzheimer's disease, gaining a new understanding of rare yet lethal prion diseases may provoke fresh insights into human dementias."

The study was funded by the Alberta Prion Research Institute, Alberta Innovates-Health Solutions, the Canada Foundation for Innovation, the US National Institutes of Health and Centers for Disease Control and Prevention, the University Health Network, and the Charles S. Britton Fund.

Bev Betkowski | EurekAlert!
Further information:
http://www.ualberta.ca

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>