Targeting GD3S to reduce plaque and improve memory
Alzheimer's disease is characterized by the accumulation of plaques in the brain, widespread neurodegeneration, and cognitive decline. We have shown that by eliminating an enzyme called GD3S we are able to reduce plaque formation, block cell death, and prevent memory deficits in a mouse model of Alzheimer's disease. This suggests that blocking GD3S may useful in treating Alzheimer's disease. However, in these mice the mutation that blocked GD3S was made before birth, and the enzyme plays an important role in many processes that are important for normal brain development. Thus it's important to test the therapy in adult mice, after they've gone through normal brain development. This is analogous to what a genetic therapy will be like for Alzheimer's patients, i.e., the treatment begins in adulthood. A new technique, called siRNA, allows us to simply and efficiently suppress the expression of the GD3S gene in live mice. We propose to use siRNA to suppress GD3S expression in a mouse model of Alzheimer's disease. Consistent with our previous results, we expect that this novel genetic therapy will significantly reduce plaque formation and completely block the memory deficits normally exhibited by these mice.
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First published on: June 10, 2008
Last modified on: September 2, 2010