Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Aberrant Tau Proteins Put Neuronal Networks to Sleep

06.10.2016

Drug “Rolofylline” a Possible Antidote

In a study published in the journal PNAS scientists of the German Center for Neurodegenerative Diseases (DZNE) present new findings on the role of the protein Tau in certain brain diseases. Their report which is based on laboratory studies suggests that the drug “Rolofylline” could possibly alleviate learning and memory problems associated with aggregating Tau proteins.


The current study shows that Tau aggregates attenuate neuronal activity. In the above image two neurons are depicted. Image: DZNE/Frank Dennissen

The brain could easily be compared to the internet. In both networks information is transmitted from one unit to the next with numerous units making up the network. Unlike computers, neurons are interconnected by axons, thin biological wires which can be as long as one meter.

A protein called Tau normally helps in maintaining axonal integrity by stabilizing the tracks which are necessary to transport cellular components within the axon. However, Tau goes astray in multiple neurodegenerative diseases like Alzheimer’s and other “tauopathies”. Here it starts to aggregate into tiny fibers or clumps, which can corrupt neuronal function. However, the underlying mechanisms are poorly understood and there is therefore no effective treatment.

Now, researchers at the DZNE and the caesar research center led by Eva-Maria and Eckhard Mandelkow shed new light on the pathological processes that involve Tau proteins. As they report in the “Proceedings of the National Academy of Sciences of the USA” (PNAS), under pathological conditions, small aggregates of Tau accumulate in the axons. As a result, neuronal activity is attenuated but neurons do not die and do not seem to be seriously ill.

The aggregates only let neurons, so to say, doze off. However, the researchers also found a potential antidote: A drug called “Rolofylline”. It re-establishes neuronal activity despite of the production of pathological Tau. Rolofylline works by enhancing signal transmission and reception which strengthens the communication between nerve cells. Consequently, Rolofylline alleviates learning and memory deficits in mice that express the aberrant Tau protein, as the scientists have revealed.

Rolofylline was originally devised to treat renal dysfunction in human heart failure patients. The drug binds to a subset of cellular sensors called “adenosine A1 receptors”. Thereby, signal pathways are blocked, that otherwise would down-regulate neuronal network activity. Patients with neurodegenerative diseases might benefit from this. “Our results suggest that Rolofylline could potentially be useful to treat neuronal dysfunctions that occur in tauopathies. This makes the drug a hot candidate for further studies.

As an analogy, the Tau aggregates resemble a concrete wall in the middle of the room which blocks a WiFi signal. Rolofylline seems to work as a WiFi booster that can re-establish the connection despite of the obstruction”, says Frank Dennissen, a member of the Mandelkow Lab and first author of the current paper.

Original publication
“Adenosine A1 receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280”, Frank J. A. Dennissen, Marta Anglada-Huguet, Astrid Sydow, Eckhard Mandelkow and Eva-Maria Mandelkow, PNAS (2016), DOI: 10.1073/pnas.1603119113

Media Relations
Dr. Marcus Neitzert
DZNE, Communications
Phone: +49 228 / 43302-267
marcus.neitzert@dzne.de

The German Center for Neurodegenerative Diseases (DZNE) investigates the causes of diseases of the nervous system and develops strategies for prevention, treatment and care. It is an institution within the Helmholtz Association of German Research Centres with nine sites across Germany (Berlin, Bonn, Dresden, Göttingen, Magdeburg, Munich, Rostock/Greifswald, Tübingen and Witten). The DZNE cooperates closely with universities, their clinics and other research facilities.

Weitere Informationen:

http://www.dzne.de/en/about-us/public-relations/news/2016/press-release-no-15.ht...
http://www.dzne.de/en | Twitter: @dzne_en | Facebook: www.dzne.de/facebook

Dr. Marcus Neitzert | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>