2022 Spring GAPNA Newsletter Volume 41 Number 1

New Strategy for Alzheimer’s Disease Treatment Targets Cell-Wide Protein Malfunction

A new strategy that targets cell-wide protein malfunction shows promise for Alzheimer’s disease and brain cancers, according to researchers. The strategy has been used to create novel biomarkers and therapeutics, with a Phase 2 clinical trial for use in Alzheimer’s disease already underway.

For a cell to be healthy, proteins need to take on the right shape and interact in specific ways. A class of molecules called chaperomes helps the proteins form correctly.

In diseases like cancer, Parkinson’s, and Alzheimer’s, chaperomes stop working normally and become poisonous, causing proteins in the cell to take on the wrong shape and interact with each other in ways that can cause disease. In cancer, for example, the malfunctioning proteins allow the cell to grow and divide in an uncontrolled way.

In Alzheimer’s, the malfunctioning proteins include those essential for memory and thinking.

Scientists developed a small molecule that targets the disease-causing chaperomes. This molecule, called PU-AD, could be used as both a biomarker and a therapeutic because it binds specifically with the faulty chaperomes.

When PU-AD is attached to a tag that can be visualized with a PET scan, it can be used as a biomarker to detect disease.

PU-AD could also be used as a drug to bind and neutralize the poisonous chaperome molecules. In the study, the scientists found PU-AD targets diseased cells but not healthy ones — an important step toward using it as both a biomarker and a therapeutic.

For details, see Bolaender, A. et al. (2021). Chemical tools for epichaperome-mediated interactome dysfunctions of the central nervous system. Nature Communications, 12(1), 4669. https://doi.org/10.1038/s41467-021-24821-2