In a recently published review, a research team led by MedUni Vienna has highlighted a promising new approach to drug discovery. The focus is on the targeted modulation of certain intracellular signalling proteins as a strategy for controlling disease-relevant signalling pathways and reducing side effects. The findings were published in the renowned journal Trends in Pharmacological Sciences and expand the range of tools available for developing personalised therapies, for example for the treatment of neurological diseases.

The team led by Christian Gruber from the Center for Physiology and Pharmacology at MedUni Vienna focused its research on so-called β-arrestins, multifunctional switching points in cellular signal transduction. These proteins regulate, amplify or direct signals within the cell, but have hardly been used as a specific target for drugs to date. However, new findings show that changes in β-arrestins can be associated with many diseases, including brain disorders.

"Our research shows how tailor-made peptides, i.e. small protein molecules generated by computational design or derived from chemical libraries, bind specifically to target structures such as receptors or arrestins. In contrast to classic active substances, which often influence cellular signals in a non-specific manner, this approach enables differentiated control of signalling pathways," explains study leader Christian Gruber.

Cyclic and nature-inspired peptides, i.e. ring-shaped molecules based on natural blueprints, are particularly promising in this context, as they are particularly stable and act precisely on defined cellular signalling processes. "In this way, our research expands the toolkit for developing precision therapies that are potentially more effective and better tolerated," Gruber and his team summarise the relevance of their work.

New perspective on neurological diseases
The targeted modulation of β-arrestins opens up new perspectives for the treatment of neurological diseases such as Alzheimer's and certain types of tumours such as glioblastoma. For peptides to be effective in these applications, they must be particularly small, stable and ring-shaped (cyclic) so that they can effectively enter the cells and, ideally, also cross the blood-brain barrier. "That's why we are already working on methods to deliver peptides specifically to their site of action in the tissue and to exert their effect as precisely as possible," says Christian Gruber in the run-up to further research work.