Researchers Design Promising Amyloid Plaque Inhibitors For Alzheimer ’s Disease

In a recent study entitled “A Hot-Segment-Based Approach for the Design of Cross-Amyloid Interaction Surface Mimics as Inhibitors of Amyloid Self-Assembly”  and published in Angewandte Chemie, a team of scientists from the Technical University of Munich (TUM) presented novel molecules that prevent amyloid protein aggregation. These findings open the door for new treatments against cell-degenerative diseases such as Alzheimer’s and type 2 diabetes.

Alzheimer’s disease is a neurodegenerative disorder that affects memory and learning neurons with severe cognitive and behavioral implications. A hallmark of Alzheimer’s is the misfolding and aggregation of amyloid-beta (Ab) protein into toxic insoluble fibrils – amyloid plaques. Researchers designed 16 different peptides and studied their efficiency in blocking the aggregation of the Ab protein and the islet amyloid polypeptide (IAPP), a molecule associated with amyloid plaque formation in type 2 diabetes.

Previous studies have determined that Ab and IAPP bind to each other, overcoming their self-aggregation into insoluble plaques. In light of this knowledge, the team designed 16 peptides containing short sequences of the IAPP protein that are known to mediate IAPP interaction with the Ab protein. From these, three peptides were effective inhibitors of both Ab and IAPP toxic aggregates; four molecules showed a selective inhibition of Ab protein self-association; and one peptide displayed a selective inhibition of IAPP aggregation.

These findings suggest that the novel class of amyloid plaque inhibitors developed by the researchers might be suitable for the development of therapeutics to combat Alzheimer’s and type 2 diabetes. Before that, the in vivo clinical efficacy of the inhibitors needs to be tested to confirm these in vitro results. The team is now developing studies to assess the therapeutic potential of these specific peptide molecules.

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