Scientists from University of Michigan have developed new molecular tools that may offer a potential treatment for Alzheimer's disease.
The team has shown how amyloid-beta peptides, which clump together to form plaques in the brain of Alzheimer's patients, may cause cell death, leading to the disease's devastating symptoms of memory loss and other mental difficulties.
AdvertisementThough the exact mechanism for amyloid-beta clump formation isn't known, scientists do know that copper and zinc ions are somehow involved, not only in the aggregation process, but apparently also in the resulting injury.
Copper, in particular, has been implicated in generating reactive oxygen species, which can cause cell damage.
One way of studying the role of metals in the process is by sopping up the metal ions with molecules called chelators and then seeing what happens when the metal ions are out of the picture.
The researchers found that removing metals, hampers both amyloid beta clumping and the production of those harmful reactive oxygen species, suggesting that chelators could be useful in treating Alzheimer's disease.
However, most known chelators can't cross the blood-brain barrier, the barricade of cells that separates brain tissue from circulating blood, protecting the brain from harmful substances in the bloodstream.
To counter the problem, researchers have developed "bi-functional" small molecules that not only grab metal ions, but also interact with amyloid-beta.
"The idea is simple," said assistant professor Mi Hee Lim, who has joint appointments in the Department of Chemistry and the Life Sciences Institute.
"We found molecules known for amyloid-beta recognition and then attached metal binding sites to them," the expert added.
The study showed that bi-functional molecules were able to regulate copper-induced amyloid-beta aggregation, not only disrupting the formation of clumps, but also breaking up clumps that already had formed.
The study appears online in the Journal of the American Chemical Society.