Alzheimer's researcher reveals a protein's dual destructiveness—and therapeutic potential

December 3, 2012 , University of British Columbia

A scientist at the University of British Columbia and Vancouver Coastal Health has identified the molecule that controls a scissor-like protein responsible for the production of plaques – the telltale sign of Alzheimer's disease (AD).

The molecule, known as GSK3-beta, activates a gene that creates a protein, called BACE1. When BACE1 cuts another protein, called APP, the resulting fragment – known as amyloid beta – forms that clump together into plaques in the brain, eventually killing .

Using an , Dr. Weihong Song, Canada Research Chair in Alzheimer's Disease and professor of psychiatry, found that disabling GSK3-beta's effect in mice resulted in less BACE1 and far fewer deposits of amyloid in their brains. Song's research, published online today in the , also found that such mice performed better than untreated mice on memory tests.

Previous research had shown that GSK3-beta spurred the growth of twisted fibers inside neurons, known as tangles – another hallmark of AD. Song says his discovery of the protein's dual destructiveness makes it a promising target for drug research.

GSK3-beta, however, is a versatile enzyme that controls many vital . The drug used to inhibit GSK3-beta in the mice is too indiscriminate, and could cause several serious side effects, including cancer.

"If we can find a way to stop GSK3-beta's specific reaction with BACE1, and still leave it intact to perform other crucial tasks, we have a much better chance of treating AD and preventing its progression," says Song, a member of the Brain Research Centre at UBC and the Vancouver Coastal Health Research Institute (VCHRI), and Director of the Townsend Family Laboratories at UBC.

Journal information: Journal of Clinical Investigation

Provided by University of British Columbia