UCSB scientists make headway in understanding Alzheimer...( (Santa Barbara Calif.) Scientists a...),Health

(Santa Barbara, Calif.) Scientists at UC Santa Barbara have discovered that a protein called BAG2 is important for understanding Alzheimer's disease and may open up new targets for drug discovery. They are ready to move from studying these proteins in culture to finding out how they work with mice.

In a paper published this week in the Journal of Neuroscience, the scientists describe important activities of BAG2 in cleaning up brain cells. The protein tau is normally found in brain cells, but scientists don't know why it clumps into tangles in people with Alzheimer's disease.

Senior author Kenneth S. Kosik, co-director of UCSB's Neuroscience Research Institute, and Harriman Chair in Neuroscience, has been involved in the study of neurons that develop neurofibrillary tangles, one of the hallmarks of the disease, since he was a postdoctoral fellow. "Early on in my career, we were one of several labs to discover that tau was in the neurofibrillary tangles," said Kosik.

Kosik's team recently started to work on BAG2 to find out how it may be involved in the removal of tangled tau. "It turns out that when you put this protein into the cell, it clears away the damaged tau very nicely," said Kosik. It doesn't clear away all the tau; it goes for the damaged tau protein and removes it.

For unknown reasons, when tau accumulates in a neurofibrillary tangle, the cell can't get rid of it. "All cells including neurons have an elaborate, sophisticated, elegant system for disposing of proteins," said Kosik. "Proteins have a certain turnover; sometimes they get damaged. The cell has its own trash can called the proteosome, and damaged proteins are deposited there.

"We've done this experiment many ways," said Kosik. "We've discovered a bit about how BAG2 works. We've turned it on to remove tau. We've turned it off to increase tau. We've really done a lot of manipulations using cell culture." So BAG2 is a new player, a new pr
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