Yale researchers identified a drinking cocktail from design molecules that hinder the key first step in Alzheimer's disease, and even recovers memories in mice, reported on Thursday Cell Reports.
The binding of amyloid beta peptides to prion proteins causes a cascade of destructive events in the progression of Alzheimer's plaque accumulation, destructive immune system response, and damage to the synapses.
"We wanted to find molecules that could have a therapeutic effect on this network," said senior author Stephen Streetmater, neurology professor of neurology, Vincent Coates, and director of the Center for Disease Research in Yale Alzheimer's.
Strittmatter and research scientist Eric Guenter displayed tens of thousands of compounds that require molecules that could interfere with the harmful prion interaction with amyloid beta. They found that an old antibiotic looked like a promising candidate, but was active only after decomposition to form a polymer. The associated small polymers retained the benefit and also managed to pass through the blood-brain barrier.
They then dissolved the optimized polymer compound and fed it with mice designed to have a condition that mimics Alzheimer's disease. They found that the brain's synapses were repaired, and the mice recovered the lost memory.
The Dartmouth University Coalition Team published a positive response when delivering the same cocktail of cells modeled as Creutzfeldt-Jakob disease, a destructive neurological condition caused by an infection with a misplaced prion protein.
The next step is to verify that the compounds are not toxic in preparing for the translation of clinical trials for Alzheimer's disease.
The research was funded by grants from NIA, NINDS, the Alzheimer's Association and the Medical Research Fund at Streetmater.
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