Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers unlock secret to mysterious movement disorder

25.11.2011
Neurodegenerative diseases represent one of the greatest challenges in our aging society. Yet research into these illnesses is difficult because of the limited availability of human brain tissue.

Fortunately, scientists at the Life & Brain Research Center and the Clinic for Neurology at the University of Bonn have discovered a way to work around the problem. By taking skin cells from patients with a genetic movement disorder and reprogramming them into so-called induced pluripotent stem cells, researchers were able to create functional neurons that allowed them to investigate the causes of the disease. Their results will be published in the journal Nature.

The focus of the Bonn study is Machado-Joseph disease, which affects people’s ability to coordinate movement. First identified among Portuguese descendants living on the Azores, today it represents the most frequent dominantly inherited cerebellar ataxia in Germany. Most patients first develop symptoms, which include difficulty walking and other neurological difficulties, between the ages of 20 and 40. The cause of the disorder is a repeating sequence in the ATXN3 gene, which causes build-up of the Ataxin protein, damaging neurons in the brain. Before the study, no one knew why the disease affected only nerve cells and what triggered the abnormal protein build-up.

“Master Cells” derived from patient skin samples

To study the disease process on a molecular level, the stem cell researcher Dr. Oliver Brüstle and his team at the University of Bonn’s Institute for Reconstructive Neurobiology derived induced pluripotent stem cells (iPS cells) from small samples of patient skin. iPS cells are cells restored to their early, undifferentiated state. Once “reprogrammed,” these “master” cells divide continuously and can transform into any cell of the body. In a subsequent step, Brüstle and his team converted iPS cells into brain stem cells, creating an ever-ready supply of neurons for their investigations.

A special feature of the neurons is that they stem from affected patients. Carrying the same genetic mutations as the patients, these neurons can serve as a cellular model for Machado-Joseph disease. “This method allows us to investigate diseased cells which we otherwise couldn’t access, almost as if we had put the patient’s brain in a Petri dish,” says Dr. Philipp Koch, a long-time colleague of Brüstle’s and one of the study’s primary authors. Together with Dr. Peter Breuer of the Clinic for Neurology at Bonn’s University Hospital, Koch sent electrical currents through the cultured neurons. The researchers showed that the formation of protein aggregate has a direct relationship with a neuron’s electrical activity. “Playing a key role is the enzyme calpain, which is activated by the increased calcium levels in stimulated neurons,” says Breuer. “This newly discovered mechanism explains why Machado-Joseph disease only affects neurons,” Brüstle explains.

Reprogramed neurons as test objects for new drugs

“The study shows the potential of this special class of stem cells for neurological research,” says Prof. Dr. Thomas Klockgether, the clinical director of the German Center for Neurodegenerative Diseases (DZNE) and director of the Clinic for Neurology at the Bonn’s University Hospital. Klockgether’s team closely collaborated with Brüstle and his researchers. For Brüstle, this was reason enough to start thinking about new organizational structures: “We need interdisciplinary departments in which scientists from stem cell biology and from molecular pathology work side by side.” Prof. Dr. Dr. Pierluigi Nicotera, the scientific director and chairman of the executive board of DZNE, endorses this view. “Cooperative structures are of great interest to DZNE,” he stresses. “Reprogramed stem cells show enormous potential for our understanding of the pathology of neurodegenerative diseases.”

In the future, Brüstle and his colleagues from the Life & Brain Research Center plan to use reprogrammed neurons to develop treatments for neurological diseases.

Publication:
Koch, P., P. Breuer, M. Peitz, J. Jungverdorben, J. Kesavan, D. Poppe, J. Doerr, J. Ladewig, J. Mertens, T. Tüting, P. Hoffmann, T. Klockgether, B. O. Evert, U. Wüllner, O. Brüstle (2011): Excitation-induced ataxin-3 aggregation in neurons from patients with Machado-Joseph disease. Nature DOI: 10.1038/nature10671
Contact:
Dr. Oliver Brüstle
Institute for Reconstructive Neurobiology
LIFE & BRAIN Center
University of Bonn
Tel: +49 (0) 228/6885-500
Email: brustle(at)uni-bonn.de

Daniel Bayer | idw
Further information:
http://www.uni-bonn.de

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>