A domestic research team has developed a new substance that can prevent the formation of amyloid beta aggregates, which cause Alzheimer's disease.
The National Research Foundation of Korea announced on the 2nd that a research team led by Professors Kim Jun-gon and Choi Tae-soo from Korea University, in collaboration with Professor William A. Goddard III's research team from the California Institute of Technology, designed a new peptide that can prevent the formation of amyloid beta aggregates, known to be a major cause of Alzheimer's disease.
Alzheimer's disease is a degenerative brain disorder that accounts for two-thirds of dementia patients, where clusters of amyloid beta and tau proteins are observed to be abnormally aggregated in the patient's brain. In particular, amyloid beta aggregates are identified as a key cause of Alzheimer's disease. Amyloid beta is originally a protein that protects nerve cells, but when it separates from the cells and forms clusters, it actually damages the nerve cells.
Antibody treatments like Leqembi and Kisunra also target amyloid beta aggregates. While peptides that bind to amyloid beta proteins and prevent aggregation have been developed, the irregular structure of amyloid beta has made peptide design difficult. To be effective, peptides need to fit precisely with the protein, but existing peptides did not match the irregular structure of amyloid beta well, resulting in low efficiency.
The research team precisely analyzed the structure of amyloid beta proteins and then designed new peptides that fit well with it. The key was to induce an 'antiparallel β–sheet' structure that could stably bind to an unstructured protein. Experimental results showed that the new peptide exhibited excellent inhibitory effects even in significantly smaller amounts.
While existing peptide inhibitors showed 56% aggregation inhibition only at 20 times the amount of amyloid beta protein, the new peptide demonstrated a 51% inhibition effect at the same concentration as amyloid beta protein and up to 84% at five times the concentration. Importantly, it was able to pass through the blood-brain barrier that protects the brain and was also found to be stable in plasma, which is the liquid component of blood, proving its potential for practical use as a therapeutic agent.
Professor Kim Jun-gon noted, "We presented a rational design method for peptides that can form stable complexes by elucidating the structural characteristics of amyloid beta proteins," adding that it would serve as an important cornerstone in the development of Alzheimer's disease treatments.
The results of this study were published in the international chemistry journal "Angewandte Chemie International Edition" on the 9th of last month.
References
Angewandte Chemie International Edition (2025), DOI: https://doi.org/10.1002/anie.202504640