The GPCR drug discovery group led by Dr. Jana Selent, publishes a study that may allow the development of new medicines or the improvement of existing ones

Press Release IMIM 04/05/2023

The journal Cell publishes a study that may allow the development of new drugs or the improvement of existing ones, taking advantage of the functioning of a specific type of protein present in the membrane of cells. This is beta arrestin, a type of molecule that acts as a controller, regulating the translation of the signal to the cell. A true 'traffic light' that acts by limiting the time in which transmitters interact and that adjusts the cell's response to its stimulus.

The work has been carried out by an international team of researchers led by the University of Birmingham, in the United Kingdom, and only one centre in Spain, the Hospital del Mar Institute for Medical Research, through the G-protein-coupled receptor-based drug development group. This group, led by Dr. Jana Selent, has provided the necessary tools to perform atomic scale simulations of the activity of molecules. Thanks to them, it has been possible to verify the regulatory role of arrestin on receptors coupled to G proteins, which can "open a way to modulate drugs more appropriately and thus improve their therapeutic profile", according to Dr. Selent.

In this study, researchers at the IMIM-Hospital de Mar, including Dr. Tomasz Stepniewski and Brian Medel Lacruz, were able to see how arrestin regulates the activity of cell receptors against stimuli (neurotransmitters or hormones) and also for how long this interaction takes place. " We have revealed the molecular mechanism that explains how beta arrestin can interact effectively with receptors to the cell membrane," Stepniewski and Medel Lacruz explain. The principal investigator, Professor of Molecular Endocrinology at the Institute of Metabolism and Systems Research at the University of Birmingham, Davide Cabeiro, explains that "acting as an air controller, these proteins feel when the receptors are activated by a hormone or neurotransmitter to modulate the signal flow between our cells".

Dr. Selent adds that "the interaction between beta arrestin and active receptors is much more dynamic than previously thought, allowing better control of signals mediated by these receptors". It should be noted that between 30 and 40% of current drugs act on G-protein-coupled receptors, precisely those regulated by beta arrestin. It is the largest group of receptors in the human body, with the primary function of regulating the effects of many hormones and neurotransmitters on cells. Thanks to this fact, beta arrestin becomes a possible target to develop new drugs or improve existing ones, regulating "in a much more adjusted way its effect and possible toxicity on cells", explains the researcher of the IMIM-Hospital de Mar.

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