Featured Research

from universities, journals, and other organizations

Researchers decode a puzzling movement disorder

Date:
November 25, 2011
Source:
Universität Bonn
Summary:
Neurodegenerative diseases represent one of the greatest challenges of our aging society. However, investigation into these diseases is made particularly difficult due to the limited availability of human brain tissue. Scientists have now taken a roundabout path: They reprogrammed skin cells from patients with a hereditary movement disorder into so-called induced pluripotent stem cells (iPS cells) and obtained functional nerve cells from them. They subsequently decoded how the disease arises.

Neurodegenerative diseases represent one of the greatest challenges of our aging society. However, investigation into these diseases is made particularly difficult due to the limited availability of human brain tissue. Scientists from the Life & Brain Research Center and Neurology Clinic of Bonn University have now taken a roundabout path: They reprogrammed skin cells from patients with a hereditary movement disorder into so-called induced pluripotent stem cells (iPS cells) and obtained functional nerve cells from them. They subsequently decoded how the disease arises.

Related Articles


Their results have now been published in the specialist periodical Nature.

The so-called Machado-Joseph disease is at the center of the current Bonn study. This is a disorder of movement coordination which was originally described in inhabitants of the Azores of Portuguese descent and which represents the most frequent dominantly inherited cerebellar ataxia in Germany today. The majority of patients develop gait abnormalities and a series of other neurological symptoms between the ages of 20 and 40. The cause of the disease is a recurring genetic sequence in the ataxin-3 gene which leads to agglutination of the corresponding protein and as a result, the nerve cells in the brain become damaged eventually. Until now, it was not clear why the disease only affects nerve cells and how the abnormal protein agglutination is triggered.

"Jack-of-all-trades" from skin specimens of patients

In order to study the disease process on a molecular level, scientists working with the stem cell researcher Prof. Dr. Oliver Brüstle at the Institute for Reconstructive Neurobiology at Bonn University initially produced so-called induced pluripotent stem cells (iPS cells) from small skin specimens from patients. These induced pluripotent stem cells are cells which are returned to a very early, undifferentiated stage. These „jacks-of-all-trades" -- once obtained -- can be multiplied to a nearly unlimited degree and they mature in all cells of the body. In the next step, the team working with Prof. Brüstle converted the iPS cells into brain stem cells from which the scientists were able to develop as many nerve cells needed for their investigations.

In particular: Since the nerve cells come from the patients themselves, they have the same genetic changes and can therefore serve as a cellular model of the disease. "This method allows us to research the disease in the cells that are actually affected and which we otherwise could not access -- almost as if we had placed the patient's brain into the cell culture dish," says Dr. Philipp Koch, a long-time colleague of Prof. Brüstle and one of the lead authors of the study. Together with his colleague Dr. Peter Breuer from the Neurology Clinic and Polyclinic of the Bonn University Medical Center, Koch electrically stimulated the artificially created nerve cells. In doing so, the researchers were able to show that the formation of the protein aggregates is directly correlated with the electrical activity of the nerve cells. "The enzyme calpain plays a key role in this; calpain is activated by the increased calcium content of stimulated nerve cells," says the biochemist Breuer. "This newly identified mechanism explains why the disease only affects nerve cells," Prof. Brüstle points out.

Reprogrammed nerve cells as a study objective for drugs

"The study illustrates the potential that this special type of stem cells has for neurological disease research," says Prof. Dr. Thomas Klockgether, Clinical Director of the German Center for Neurodegenerative Diseases (DZNE) and Director of the Bonn University Clinic for Neurology, whose team closely collaborated in this study with the scientists working with Prof. Brüstle. For Prof. Brüstle, this is reason enough to contemplate new configurations: "We need interdisciplinary departments in which scientists from stem cell biology and molecular disease research work together side by side." Prof. Dr. Dr. Pierluigi Nicotera, scientific chairman and chief executive of the DZNE, concurs: "The DZNE is very interested in cooperative arrangements. Because reprogrammed stem cells have enormous potential for understanding the pathology of neurodegenerative diseases."

As a next step, Prof. Brüstle and his colleagues from Life & Brain want to use reprogrammed nerve cells for the development of active substances to treat neurological diseases.


Story Source:

The above story is based on materials provided by Universität Bonn. Note: Materials may be edited for content and length.


Journal Reference:

  1. Philipp Koch, Peter Breuer, Michael Peitz, Johannes Jungverdorben, Jaideep Kesavan, Daniel Poppe, Jonas Doerr, Julia Ladewig, Jerome Mertens, Thomas Tüting, Per Hoffmann, Thomas Klockgether, Bernd O. Evert, Ullrich Wüllner, Oliver Brüstle. Excitation-induced ataxin-3 aggregation in neurons from patients with Machado–Joseph disease. Nature, 2011; DOI: 10.1038/nature10671

Cite This Page:

Universität Bonn. "Researchers decode a puzzling movement disorder." ScienceDaily. ScienceDaily, 25 November 2011. <www.sciencedaily.com/releases/2011/11/111124150749.htm>.
Universität Bonn. (2011, November 25). Researchers decode a puzzling movement disorder. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2011/11/111124150749.htm
Universität Bonn. "Researchers decode a puzzling movement disorder." ScienceDaily. www.sciencedaily.com/releases/2011/11/111124150749.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) — It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) — More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) — In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) — The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins