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Chemical decoy shows promise for slowing Alzheimer's by acting as decoy

rculating through the bloodstream, but only certain species are thought to be toxic. It is the diffusible beta amyloid species tiny proteins that can easily reach the brain that are thought to be toxic in Alzheimer's and associated with brain cell death and neurodegeneration.

In the current study, Good and her associates found evidence that beta amyloid preferentially binds to sialic acids, naturally occurring sugars that have increasingly been shown to be involved in many cell activities, including signaling and differentiation. Sialic acids are particularly abundant on the surfaces of brain cells but also found in lower amounts in the rest of the body. The researchers theorized that creating a polymer that acts like the surface of a brain cell, with its abundance of sialic acids, could lure toxic beta amyloid out of circulation and prevent its accumulation and binding to actual brain cells. If beta amyloid doesn't bind to the brain cells, most scientists believe that it won't be able to kill the brain cells, the researchers say.

Good's group then designed a group of synthetic, star-shaped polymers with surface sialic acids to mimic the molecules found on brain cell surfaces. Using a human neuron-derived cell line, the researchers showed in test tube studies that addition of the polymer serves as an effective "decoy" for attracting the circulating beta amyloid proteins away from the neuron-like cells. The resulting polymer-amyloid complex can then be broken down and removed by specialized cells in the brain, the researcher theorizes.

Because the decoy molecules look like components of normal human brain cells, they will hopefully be less likely to cause side effects, which have plagued many promising Alzheimer's drug candidates, Good says. She notes, for instance, that experimental vaccines targeting beta amyloid proteins have been tried in animals, but these have triggered severe immune responses that have prevented their use.

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17-Mar-2005


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