New findings on the development of Alzheimer's disease

The researchers wanted to use their study to better understand how cell membranes in the body influence the structure of peptides - molecules made up of amino acids - and their aggregation. To do this, they used model systems that they can control well experimentally. First author Dr Torsten John, who completed his doctorate in Leipzig under the supervision of Prof. Dr Bernd Abel and is now a researcher at the Massachusetts Institute of Technology (MIT) in the USA, explains: "Stress leads to oxidative processes in the body and thus changes the chemical composition of membranes. In our experiments, we compared the effects of oxidised membranes with those that were not altered. The scientists combined both biophysical laboratory experiments and computer simulations to better understand peptide aggregation. „Computer simulations, so-called molecular dynamics simulations, provide molecular insights into the mechanisms of interactions between membranes and peptides,“ says Prof Abel.

It was already known that membrane composition plays an important role in the aggregation of peptides. However, the role of oxidised membranes has been little studied to date. The researchers discovered that the effects differ between the peptides. One of the peptides studied (Aβ40), which is associated with Alzheimer's disease, aggregated faster in the presence of all membranes. In contrast, the aggregation of another peptide (Uperin 3.5) was completely prevented in the presence of the same amount of oxidised membranes. Prof Abel explains: „Depending on the properties of the peptide, including its charge, its attraction to the membrane changes, and thus the strength of the influence. If the peptides accumulate on the membrane surface, this accelerates their assembly and aggregation. However, if the attraction is very strong and they change their structure into a helix, they can no longer aggregate.

For their study, the scientists deliberately chose peptides that aggregate in a similar way but have a different origin. Aβ40 is known to be deposited in the brains of Alzheimer's patients, whereas Uperin 3.5 is an antimicrobial peptide first discovered in an Australian crustacean species. The researchers led by cooperation partner Prof. Dr Lisandra L. Martin from Monash University in Australia had previously reported on possible links between the aggregation of peptides in neurodegenerative diseases and the antimicrobial properties of the peptides. The study published in the journal „Chemical Science“ further discusses the functional role of amyloid peptides. The research work was carried out as part of the DFG Collaborative Research Centre SFB TRR 102 „Polymers under constraint: constrained and controlled molecular order and mobility“.

Press release of the "idw - Informationsdienst Wissenschaft" from 6 March 2023