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 Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>