Matthias Preusser elected Executive Editor of Neuro-Oncology Oncologist from MedUni Vienna takes on a role on the editorial board of the international journal
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Significant increase in addictions in Austria - New book "Sucht. Neue Erkenntnisse und Behandlungswege" is published by MANZ-Verlag as part of MedUni Vienna's "Health Knowledge" series
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Novel therapeutic approach for malignant pediatric brain tumor
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Molecular light switches allow insights into the central nervous system
Pharmacy has long tried to help people with neuropsychiatric problems with drugs. Due to the complexity of the brain, however, many questions remain unanswered. It is known that so-called GABAA receptors play an important role in diseases such as anxiety disorders, epilepsy, schizophrenia and autism. These proteins are found in the cell membrane of nerve cells in the brain and spinal cord. Of the myriad subtypes of these receptors, many contribute to central nervous system inhibition.
Drug development using fluorescent dyes
In order to achieve a targeted anti-anxiety, muscle-relaxing or sedative effect, the functionality of the GABAA receptors can be increased by medication. In order to improve this type of medication and to develop new ones, scientists use so-called fluorescent dyes. Under the influence of light, these molecules can be compared to a switch. The present study examines a specific molecule that is dark in solution (“lights off”) but fluoresces green (“lights on”) when bound to a GABAA receptor.
The dye under study competes with the natural neurotransmitter for binding to the receptor. Drugs with a positive impact on GABAA receptors increase the affinity of the neurotransmitter, and therefore decrease fluorescence. It is easy to observe through a microscope how the light emitted by the dye is switched off. The molecule is therefore very well suited for examining the effects of potential new drugs on GABAA receptors.
"Switch mechanism" of a dye clarified
Although the dye was described several years ago, the exact mechanism by which the fluorescence is switched on and off was still unclear. In the present study, the scientists have now discovered with the help of computer simulations that the secret lies in the spatial arrangement of the dye: in solution, the molecule is folded up like a sheet of paper. Upon binding to the receptor, it unfolds, ultimately allowing for the fluorescence that is quenched in the folded form.
The researchers' results form the basis for the development and improvement of other dyes and thus make an important contribution to pharmaceutical research.
Published in:
Applied Chemistry
Nadja K. Singer, Pedro A. Sánchez-Murcia, Margot Ernst, Leticia González: "Unraveling the Turn-on Fluorescence Mechanism of a Fluorescein-based Probe in GABAA Receptors". In: Angew. Chem. Int. Ed. 2022, e202205198; Angew. Chem. 2022, e202205198.DOI: 10.1002/anie.202205198
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