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Aberrant tau proteins put neuronal networks to sleep

Date:
October 7, 2016
Source:
Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. - German Center for Neurodegenerati
Summary:
Researchers 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.
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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 (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.


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Materials provided by Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. - German Center for Neurodegenerati. Note: Content may be edited for style and length.


Journal Reference:

  1. Frank J. A. Dennissen, Marta Anglada-Huguet, Astrid Sydow, Eckhard Mandelkow, Eva-Maria Mandelkow. Adenosine A1receptor antagonist rolofylline alleviates axonopathy caused by human Tau ΔK280. Proceedings of the National Academy of Sciences, 2016; 201603119 DOI: 10.1073/pnas.1603119113

Cite This Page:

Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. - German Center for Neurodegenerati. "Aberrant tau proteins put neuronal networks to sleep." ScienceDaily. ScienceDaily, 7 October 2016. <www.sciencedaily.com/releases/2016/10/161007084622.htm>.
Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. - German Center for Neurodegenerati. (2016, October 7). Aberrant tau proteins put neuronal networks to sleep. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2016/10/161007084622.htm
Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. - German Center for Neurodegenerati. "Aberrant tau proteins put neuronal networks to sleep." ScienceDaily. www.sciencedaily.com/releases/2016/10/161007084622.htm (accessed May 23, 2017).

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