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A research team led by the Molecular and Cellular Neurobiotechnology group at the Institute for Bioengineering of Catalonia (IBEC), in collaboration with Míriam Royo's laboratory at the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), the University of Barcelona (UB) and the Institute for Research in Biomedicine (IRB Barcelona), has identified a synthetic peptide that reduces the production of amyloid beta (Aβ).

This protein builds up in the brain in Alzheimer's disease. The work, published in the journal Bioorganic Chemistry, was carried out in cultured neurons (in vitro) and in a mouse model of the disease (in vivo).

An enzyme, BACE1, is involved in the production of Aβ. Enzymes are proteins that facilitate chemical reactions in cells; in this case, BACE1 acts like a pair of "scissors" that cuts another protein, giving rise to amyloid beta. Drugs designed to block it completely have not succeeded in clinical trials, partly because of the side effects of also blocking other necessary functions of the enzyme.

The team tried a different strategy: They designed peptides, short chains like those that make up proteins, and modified them chemically so that the body does not break them down quickly and so that they can enter cells, where amyloid beta is produced.

"We analyzed a library of 50 of these molecules in cultured neurons. P33 stood out because it clearly reduced amyloid beta without damaging the cells and, in addition, selectively slowed down BACE1 activity," explains Dayaneth Jácome, first author of the study and a researcher at IBEC.

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