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04/24/2025 10:31

Preventing harmful protein aggregation: Synthetic Peptides as basis for multifunctional drugs in Parkinson's disease

Anja Lapac Corporate Communications Center
Technische Universität München

    In Alzheimer's, Parkinson's, and type 2 diabetes, harmful protein aggregates and deposits, known as amyloid plaques, develop. There is also much evidence that these three diseases are interconnected and mutually reinforcing. A research team led by the Technical University of Munich (TUM) has now shown that synthetic mini-proteins (macrocyclic peptides) developed by the researchers inhibit both amyloid formation in Parkinson's and harmful protein interactions between the three diseases in experimental models. They could serve as the basis for future drugs to treat these diseases.

    To date, no medication can prevent the development of Alzheimer's, Parkinson's, or type 2 diabetes. Yet the urgency to take action is high because as life expectancy increases, so does the number of people who develop one of these diseases in the course of their lives. In addition, recent research has shown complex connections between the three diseases. For example, patients with type 2 diabetes have an increased risk of developing Parkinson's or Alzheimer's disease as well. Furthermore, interactions between the amyloid-forming proteins of the individual diseases can accelerate and intensify the damaging protein aggregation in the other diseases.

    In experimental models, a team led by Aphrodite Kapurniotu, Professor of Peptide Biochemistry at TUM, has now succeeded in inhibiting the formation of protein aggregates in Parkinson's disease with the help of so-called macrocyclic peptides. Moreover, these peptides also suppress harmful interactions between the proteins of the three diseases. They mimic certain features in the structure of one of the proteins. This enables them to dock onto amyloid-forming proteins of the three diseases. Their interactions are blocked and amyloid formation is prevented.

    Potential for Alzheimer's and type 2 diabetes

    With this discovery, the researchers are building on earlier studies. In these, they used the peptides in experimental models to prevent the formation of amyloid protein aggregates, which occur in Alzheimer's disease and type 2 diabetes.

    Patent applications have already been filed. "Further research is needed before suitable drugs can be launched. However, we think that our peptides are valuable candidates for the development of effective drugs for treating Parkinson's, Alzheimer's, diabetes, and their co-occurrence," says Aphrodite Kapurniotu.

    - The team collaborated with the research groups of Prof. Hilal A. Lashuel (EPFL), Prof. Dr. Jürgen Bernhagen (LMU University Hospital Munich, LMU), Dr. Regina Feederle (Helmholtz Center Munich German Research Center for Environmental Health), PD Dr. Thomas Koeglsperger and Prof. Dr. Günter Höglinger (LMU University Hospital Munich, LMU) and Prof. Dr. Gerhard Rammes (TUM University Hospital).
    - The research work was primarily funded by the German Research Foundation (DFG) as part of the SFB 1035 (spokesperson Prof. Dr. Johannes Buchner, TUM).


    Contact for scientific information:

    Prof. Dr. Aphrodite Kapurniotu
    Technical University of Munich
    Professorship Peptide Biochemistry
    Phone: +49 8161-71 5342
    akapurniotu@tum.de
    https://www.mls.ls.tum.de/pbch/home/


    Original publication:

    Hornung, S., Vogl, D. P., Naltsas, D., et al.: A. Multi-Targeting Macrocyclic Peptides as Nanomolar Inhibitors of Self- and Cross-Seeded Amyloid Self-Assembly of α-Synuclein. (2025) Angew Chem Int, https://doi.org/10.1002/anie.202422834


    More information:

    https://www.tum.de/en/news-and-events/all-news/press-releases/details/synthetic-... This news release at tum.de


    Images

    Prof. Aphrodite Kapurniotu and members of her researchteam
    Prof. Aphrodite Kapurniotu and members of her researchteam
    Astrid Eckert
    Astrid Eckert / TUM

    Prof. Dr. Aphrodite Kapurniotu
    Prof. Dr. Aphrodite Kapurniotu
    Astrid Eckert
    Astrid Eckert / TUM


    Criteria of this press release:
    Journalists, Scientists and scholars, Students
    Chemistry, Medicine
    transregional, national
    Research results
    English


     

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