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09.12.2024 14:14

Advance in pain relief research – Naturally occurring hederagenin binds to pain regulation receptor

Susann Sika Stabsstelle Universitätskommunikation / Medienredaktion
Universität Leipzig

    A team of scientists led by Professor Annette Beck-Sickinger from the Institute of Biochemistry at Leipzig University has made an important advance in pain relief research. They discovered that hederagenin, a naturally occurring substance found in the medicinal plant ivy, binds to the pain regulation receptor. Extracts of ivy (Hedera helix) have antispasmodic and analgesic effects in phytomedicine. In the search for selective inhibitors of the protein neuropeptide FF receptor 1, which is relevant for human pain regulation, the researchers discovered that hederagenin is well suited for this purpose. They have now published their findings in the journal Angewandte Chemie International Edition.

    Neuropeptide FF receptor 1 (NPFFR1) is a G protein-coupled receptor (GPCR) involved in the signalling of various physiological processes in the human body. In recent years, it has been discovered that this protein is mainly found in the spinal cord and in areas of the brain involved in pain perception. Blocking this receptor could help treat chronic pain. This has not been possible until now because NPFFR1 has many similar relatives.

    Two scientists from Beck-Sickinger’s research group tested thousands of substances. Michael Schaefer, Professor of Pharmacology at the Faculty of Medicine, provided a screening platform for this purpose. The researchers came across the naturally occurring substance hederagenin. They characterised the binding mode of the inhibitor in detailed in vitro studies. Computer modelling of the three-dimensional receptor-inhibitor complex by Professor Jens Meiler’s group at the Institute for Drug Discovery confirmed this insight.

    “These findings make a significant contribution to understanding the activation mechanism of NPFFR1 and may facilitate the rational design of future therapeutics for chronic pain. They demonstrate the importance of basic research in translating findings into applications,” says Professor Beck-Sickinger. The work was carried out as part of Collaborative Research Centre 1423, Structural Dynamics of GPCR Activation and Signaling. This research success was only possible thanks to close collaboration between the various working groups at Leipzig University, as is made possible by such a Collaborative Research Centre.


    Wissenschaftliche Ansprechpartner:

    Professor Annette Beck-Sickinger
    Institute of Biochemistry
    Phone: +49 341 97-36901
    EMail: abeck-sickinger@uni-leipzig.de

    Hannah Lentschat
    Institute of Biochemistry
    Phone: +49 341 97-36793
    EMail: hannah.lentschat@uni-leipzig.de


    Originalpublikation:

    Publication in „Angewandte Chemie International Edition“:
    Hederagenin is a Highly Selective Antagonist of the Neuro­peptide FF Receptor 1 that Reveals Mechanisms for Subtype Selectivity, Doi: 10.1002/anie.202417786
    https://onlinelibrary.wiley.com/doi/10.1002/anie.202417786


    Weitere Informationen:

    https://research.uni-leipzig.de/sfb1423/


    Bilder

    Hederagenin blocks the activation of the neuropeptide FF receptor 1, a protein found mainly in the spinal cord and areas of the brain involved in pain perception.
    Hederagenin blocks the activation of the neuropeptide FF receptor 1, a protein found mainly in the s ...
    Graphic: Hannah Lentschat


    Merkmale dieser Pressemitteilung:
    Journalisten, Wissenschaftler
    Biologie, Chemie, Medizin
    überregional
    Forschungsergebnisse, Wissenschaftliche Publikationen
    Englisch


     

    Hederagenin blocks the activation of the neuropeptide FF receptor 1, a protein found mainly in the spinal cord and areas of the brain involved in pain perception.


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