Understanding of Alzheimer's disease

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Scientists at UC Santa Barbara have discovered that a protein called BAG2 is important in the understanding of 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 in mice. In a paper published this week in the Journal of Neuroscience, the scientists describe important role 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. "Early on in my career, we were one of several labs to discover that tau was in the neurofibrillary tangles," said team leader. The 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," he said. 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. 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. There is nothing about a drug or a treatment in any of these findings; however, the first step in fighting any illness is finding what you want to target the drug to," said the team leader. "This is a protein that is involved in neurofibrillary tangles, so now we have a new target for drug discovery. This is not a drug or a treatment, just a new target. The new target is BAG2." They are looking forward to studying BAG2 in mice.

The team leader explained that we all have these proteins in our cells; however, they can go awry. Their levels can be off, or they may malfunction in another way. The same normal protein can begin to malfunction. "It may be that BAG2 is not doing its job right; it may be that BAG2 is overwhelmed, because sometimes tau is building up, and there is not enough BAG2 there. "We cannot conclude from this that BAG2 is the fundamental problem in the disease state. It is only a possible target that can help us find our way out of the disease."

However, the current project started when he and his team suspected that a key to understanding Alzheimer's disease was finding out why the cell fails to degrade tau and dispose of it. They knew, even before starting the project, that the cell has marked the tau protein in Alzheimer's disease for degradation. There is a marker on the tau protein in the neurofibrillary tangles, which indicates that this is a protein that should go to the trash. The marker is called ubiquitin. "We knew something was going on there," said he. "CHIP has a dual function. It calls out to the cell and says there is a protein here that is at a critical juncture. If the protein is salvaged, then CHIP goes off tau, and tau goes back to being a normal protein. But if the protein cannot be salvaged because it is so badly damaged, then CHIP goes into action and marks the tau for degradation by putting on several ubiquitins, and that's the signal to go to the trash." ...http://www.medicalnewstoday.com

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Belgian hi-tech ingredient developer, KitoZyme, says its fungi-sourced version of the weight management ingredient, chitosan, will be commercially available in food supplements in 2009. ...http://www.nutraingredients.com

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