Preventing harmful protein aggregation: Synthetic peptides as the basis for multifunctional drugs in Parkinson’s disease

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.

In a study appearing in Angewandte Chemie International Edition, a research team led by the Technical University of Munich (TUM) has 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.

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 Kapurniotu.