TUM Breakthrough: Synthetic Peptides Disrupt Protein Aggregation Across Parkinson’s, Alzheimer’s, and Diabetes

TUM Breakthrough: Synthetic Peptides Disrupt Protein Aggregation Across Parkinson’s, Alzheimer’s, and Diabetes

(IN BRIEF) A team at the Technical University of Munich has developed synthetic macrocyclic peptides that inhibit harmful protein aggregation linked to Parkinson’s disease. The peptides also block the interactions between proteins involved in Alzheimer’s and type 2 diabetes, which often accelerate disease progression when combined. These multifunctional peptides could form the basis of future drugs targeting all three conditions. The study builds on earlier work and demonstrates potential for broad therapeutic applications in age-related diseases.

(PRESS RELEASE) MUNICH, 24-Apr-2025 — /EuropaWire/ — A research team at the Technical University of Munich (TUM) has made a promising breakthrough in tackling Parkinson’s disease by developing macrocyclic peptides—small synthetic proteins—that inhibit the formation of harmful amyloid aggregates. These same peptides also suppress damaging interactions among the proteins responsible for Parkinson’s, Alzheimer’s, and type 2 diabetes, offering hope for a future class of multifunctional drugs targeting multiple neurodegenerative and metabolic disorders simultaneously.

Protein aggregation, a hallmark of Parkinson’s and Alzheimer’s diseases as well as type 2 diabetes, leads to the formation of amyloid plaques in the body. These diseases are often interlinked; people with type 2 diabetes face a higher risk of developing Alzheimer’s or Parkinson’s, and the protein interactions between the diseases can exacerbate symptoms and progression.

In laboratory experiments, the TUM team—led by Professor Aphrodite Kapurniotu from the TUM School of Life Sciences—successfully used these macrocyclic peptides to inhibit both the aggregation of α-synuclein, the key amyloid-forming protein in Parkinson’s, and the cross-seeding effects among the proteins associated with the three diseases.

The peptides are engineered to imitate specific structural elements of amyloidogenic proteins. By doing so, they bind to those proteins and disrupt the process that leads to amyloid plaque formation. This research builds on earlier findings in which the same class of peptides blocked aggregation in Alzheimer’s and diabetes models.

Patent filings are already underway. Although clinical applications are still on the horizon, the researchers believe these macrocyclic peptides hold significant potential to serve as a foundation for next-generation drugs that address not just single diseases, but the overlapping biochemical mechanisms of several age-related disorders.

The research was conducted in collaboration with experts from EPFL, LMU University Hospital Munich, Helmholtz Center Munich, and TUM University Hospital, and was primarily funded by the German Research Foundation (DFG) under the SFB 1035 program.

Publications

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

Spanopoulou, A., Heidrich, L., Chen, H. R., et al.: A. Designed Macrocyclic Peptides as Nanomolar Amyloid Inhibitors Based on Minimal Recognition Elements. (2018) Angew Chem Int,  https://doi.org/10.1002/anie.201802979

Further information and links

• Aphrodite Kapurniotu is a Professor of Peptide Biochemistry at the TUM School of Life Sciences.
• 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).

Media Contacts:

Anja Lapac
Corporate Communications Center
presse@tum.de

Contacts to this article:

Prof. Dr. Aphrodite Kapurniotu
Technical University of Munich
Professorship of Peptide Biochemistry
Tel.: +49 8161-71 3542
akapurniotu@tum.de

SOURCE: Technical University of Munich