"Nature" publication gives hope to a more targeted effect of medicine
International scientists led by Carsten Hoffmann and Martin Lohse of the University Würzburg, Germany, identified for the first timeβ-Arrestin as an independent signaling molecule. The protein modulates a pharmaceutically important pathway. The results were published in the prestigious scientific journal "Nature". It leads to new drug targets, for example in pain therapy.
The most important target for drug research are G-protein coupled receptors (GPCR). Around 30 percent of all medicine work on more than 800 members of this class of proteins. GPCRs are crucial for cell communication and the processing of pain and sensory stimuli.
The protein β-Arrestin regulates GPCR. However, it remained unclear how it functions on a molecular level. With biosensors, scientists were able to explain the interaction on a temporal and spatial level. "When I discovered β-Arrestin in 1990, it looked like, it is there to disable receptors," said Lohse. "That it acts as an independent signaling molecule, we could demonstrate only now with the latest technology."
Experiments showed that β-Arrestin was transferred into an active state by receptors, which lasted longer that its interaction with the receptor. The change was so significant that a cycle of activation and deactivation of β-Arrestin was detectable - a criterion for the definition of an independent signaling molecule. At the same time, American collaborators were able to show that the type of activation of β-Arrestin depends on the activating receptor.
Their results will be also published in "Nature". The exchange with American colleagues pushed the project enormously. Hoffmann became aware of their work during a conference. "This project went through ups and downs," Hoffmann remembers. "We often had to be patient, but it was worth it."
By molecular reinforcing or blocking of β-Arrestin, the effect of future drugs could be more specific and associated with fewer side effects. Due to their diversity, GPCR and now possibly β-Arrestin are important targets for pharmaceutical substances. Hoffmann expects a particularly good progress in long-term treatment with strong painkillers.
The body gets used to the medicine and becomes increasingly depended on higher doses. At the same time, side effect will appear even stronger. New medicine targeting specifically β-Arrestin on a molecular level could minimize this tolerance and therefore its side effects, and could enable a more effective long-term therapy.
Hoffmann is optimistic about future projects. As a next step, he wants to test whether activation of β-Arrestin can be changed by model substances. "That would be the first step to new medical drugs."
Publication: Susanne Nuber, Ulrike Zabel, Kristina Lorenz, Andreas Nuber, Graeme Milligan, Andrew B. Tobin, Martin J. Lohse, Carsten Hoffmann β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle. Nature doi:10.1038/nature17198
Prof Carsten Hoffmann joined the Rudolf Virchow Center for Experimental Biomedicine of the University of Würzburg in 2012.
Prof Martin Lohse is founder and chair of the Rudolf Virchow Center and future scientific manager and chairman of the Max Delbück Center for Molecular Medicine (MDC) in Berlin.
Research group Hoffmann:
Research group Lohse:
The Rudolf Virchow Center for Experimental Biomedicine is a central institution of the University of Würzburg. Research groups are working on target proteins, which are essential for cellular function and therefore central to health and disease.
Prof. Dr. Carsten Hoffmann
Tel. 0049 (0)931 3148304, firstname.lastname@example.org
Prof. Dr. Martin Lohse
Tel. 0049 (0)931 3148400, email@example.com
Dr. Daniela Diefenbacher (Press Office, Rudolf Virchow Center)
Tel. 0049 (0)931 3188631, firstname.lastname@example.org
Dr. Daniela Diefenbacher | idw - Informationsdienst Wissenschaft
Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences
Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...
The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...
At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.
When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...
At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.
Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...
16.03.2018 | Event News
13.03.2018 | Event News
08.03.2018 | Event News
16.03.2018 | Earth Sciences
16.03.2018 | Physics and Astronomy
16.03.2018 | Life Sciences