Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mad cow protein aids creation of brain cells

14.02.2006


Few conditions are more detrimental to human brains than the one popularly referred to as mad cow disease. But now there’s reason to suspect that the protein which, when malformed, causes bovine spongiform encephalopathy in cows and Creutzfeldt-Jakob disease in people, might also be necessary for healthy brain function. Researchers from Whitehead Institute for Biomedical Research and Harvard Medical School/Massachusetts General Hospital have discovered that the normal form of this detrimental protein may actually help the brain create neurons, those electricity-conducting cells that make cognition possible.



"It’s been difficult to understand why this prion protein, which when malformed subjects us to this horrible disease, is so abundant in our brains in the first place," says Whitehead Member Susan Lindquist, who is also a professor of biology at MIT. Along with Jeffrey Macklis of Harvard Medical School and Massachusetts General Hospital, she is co-senior author on this Proceedings of the National Academy of Sciences paper, scheduled to be published the week of February 13. "We’ve known for years what happens when this protein goes wrong. Now we’re starting to see what its normal form does right."

For over ten years, researchers have known that a protein called PrP causes mad cow disease and its human equivalent, Creutzfeld-Jakob disease, when it forms incorrectly. PrP is a prion, a class of proteins that has the unusual ability to recruit other proteins to change their shape. (PrP is shorthand for "prion protein".) This is significant, because a protein’s form determines its function. When a prion changes shape, or "misfolds," it creates a cascade where neighboring proteins all assume that particular conformation. In some organisms, such as yeast cells, this process can be harmless or even beneficial. But in mammals, it can lead to the fatal brain lesions that characterize diseases such as Creutzfeld-Jakob.


Curiously, however, PrP can be found throughout healthy human bodies, particularly in the brain. In fact, it’s found in many mammalian species, and only on the rarest occasions does it misfold and cause disease. Clearly, scientists have reasoned, such a widely conserved protein also must play a beneficial role.

In 1993, scientists created a line of mice in which the gene that codes for PrP was knocked out, preventing the mice from expressing the prion in any tissues. Surprisingly, the mice showed no sign of any ill effect. The only difference between these mice and the control mice was that the knock-out animals were incapable of contracting prion-related neurodegenerative disease when infected. Researchers knew then that PrP was necessary for mad-cow type diseases; any other kind of normal function remained unknown.

Recently, researchers from the labs of Lindquist and Whitehead Member Harvey Lodish discovered that PrP helps preserve stem cells in the blood. Because of this, Lindquist teamed up with Macklis to see if there might also be a similar connection between PrP and cells in the brain, where the prion protein is far more abundant.

Andrew Steele, a graduate student from the Lindquist lab, teamed up with Jason Emsley and Hande Ozdinler, postdoctoral researchers in the Macklis lab, to investigate the effects PrP might have on neurogenesis. (Neurogenesis is the process by which the brain creates new neurons in the developing embryonic brain and, to a limited extent, even in the adult brain.) To do this they studied embryonic brain tissue from three kinds of mice: those in which the PrP gene was permanently disabled, or knocked out; those in which the gene was over-expressed, producing an unusually large amount of PrP; and normal control mice.

Steele and Emsley isolated neural precursor cells--early stage cells that give rise to mature neurons and so-called glial support cells. (These precursor cells are often referred to as neural stem cells, though they lack certain properties that are characteristic of broader stem cells.) After placing these embryonic precursor cells under culture conditions that enabled them to grow and differentiate, they noticed striking differences. Cells from the knock-out mouse remained in the precursor stage for a long time, compared to the control mice. But cells in which PrP was over-expressed began forming mature neurons almost immediately.

"The more PrP you have, the faster you become a neuron. The less you have, the longer you’ll stay in a precursor state," says Steele.

In addition, the researchers discovered that in adult mouse brains, PrP is only expressed in neurons, but not in the glial cells, cells that form the brain’s connective tissue. They also found that while the amount of PrP does affect the speed with which neurons were produced in the adult brain, ultimately the different mice ended up with the same number of neurons. In order to further investigate these findings, the researchers are currently placing these different groups of mice in stimulation-rich environments that will require the quick production of new neurons. The idea is to observe the mice and see if there are any significant differences in how they perform and behave.

"We now see that the normal form of this prion protein is one of many key players in the fascinating and important process of neurogenesis," says Macklis, who is also a member of the Harvard Stem Cell Institute.

David Cameron | EurekAlert!
Further information:
http://www.wi.mit.edu

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>