A research team at the Technical University of Munich (TUM) has developed macrocyclic peptides that can prevent harmful protein aggregation associated with Parkinson’s, Alzheimer’s, and type 2 diabetes. These synthetic mini-proteins have shown promising effects in initial experiments and could pave the way for the development of multifunctional therapeutics.
In Alzheimer's, Parkinson's, and type 2 diabetes, harmful protein aggregates and deposits, known as amyloid plaques, develop. Scientists at Technical University of Munich (TUM) have now created synthetic mini-proteins, known as macrocyclic peptides, that not only inhibit amyloid formation in Parkinson’s disease models but also disrupt pathological protein interactions between the three diseases. These peptides could serve as a foundation for next-generation multifunctional drugs.
To date, there is no therapy capable of preventing the onset of these diseases - yet the need for action is urgent. As life expectancy increases, so does the number of individuals affected. Recent research shows that Parkinson’s, Alzheimer’s, and type 2 diabetes are interconnected: individuals with type 2 diabetes have a higher risk of also developing Parkinson’s or Alzheimer’s. Moreover, interactions between amyloid-forming proteins may accelerate and intensify disease-related protein aggregation.
The team led by Aphrodite Kapurniotu, Professor of Peptide Biochemistry at TUM, has demonstrated in model systems that macrocyclic peptides can suppress the formation of protein aggregates in Parkinson’s and simultaneously mitigate harmful protein interactions across the three diseases. The peptides mimic specific structural features of one of the involved proteins, allowing them to bind to amyloid-forming proteins from the different diseases. This binding blocks their interaction and prevents the formation of amyloid structures.
These findings build upon the team’s earlier work, which showed that the peptides can also prevent the formation of amyloid aggregates associated with Alzheimer’s and type 2 diabetes in experimental models.
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.