Compounds that have the potential to delay or treat Alzheimer's disease and other degenerative disorders were identified by scientists.
The research, led by David Eisenberg, director of the UCLA-Department of Energy Institute of Genomics and Proteomics and a Howard Hughes Medical Institute investigator, report the first application of "structure-based" technique in the search for molecular compounds that bind to and inhibit the activity of the amyloid-beta protein responsible for forming dangerous plaques in the brain of patients with Alzheimer's and other degenerative diseases.
Amyloid fibrils are elongated, rope-like structures, linked protein molecules that form in the brains of patients.
The researchers conducted a computational screening of 18,000 compounds in search of those most likely to bind tightly and effectively to the protein.
Those compounds that showed the strongest potential for binding were then tested for their efficacy in blocking the aggregation of amyloid-beta and for their ability to protect mammalian cells grown in culture from the protein's toxic effects, which in the past has proved very difficult.
Ultimately, the researchers identified eight compounds and three compound derivatives that had a significant effect.
While these compounds did not reduce the amount of protein aggregates, they were found to reduce the protein's toxicity and to increase the stability of amyloid fibrils- a finding that lends further evidence to the theory that smaller assemblies of amyloid-beta known as oligomers, and not the fibrils themselves, are the toxic agents responsible for Alzheimer's symptoms.
The researchers hypothesize that by binding snugly to the protein, the compounds they identified may be preventing these smaller oligomers from breaking free of the amyloid-beta fibrils, thus keeping toxicity in check.
The research was published in journal eLife.