protein in the brain 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.
‘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.’
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
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.
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