The researchers used a fluorescent sensor for amyloid beta assemblies, called thioflavin T, to show that the assemblies were broken up in the presence of midkine. Modeling of those data revealed that midkine inhibits amyloid beta elongation and secondary nucleation, two specific phases during assembly formation. Nuclear magnetic resonance confirmed this finding.
“Once the amyloid beta assemblies grow, the signal becomes weaker and broader until it disappears because the technique can only analyze small molecules,” said Peng. “But when we add in midkine, the signal returns, showing that it inhibits the large assemblies.”
Additionally, the researchers used Alzheimer’s disease mouse models that have increased amyloid beta and demonstrated that removing the midkine gene resulted in even higher levels of amyloid beta assemblies. These results point to the protective role the protein has against Alzheimer’s disease.
The researchers have opened a potential avenue for drug discovery by identifying the apparent protective role of midkine. “We want to continue to understand how this protein binds to amyloid beta so we can design small molecules to do the same thing,” said Peng. “With this work, we hope to provide strategies for future treatment.”
Reference: Zaman M, Yang S, Huang Y, et al. Midkine attenuates amyloid-β fibril assembly and plaque formation. Nat Struct Mol Biol. 2025. doi: 10.1038/s41594-025-01657-8
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.