Scientists at UCSB’s Neuroscience Research Institute have made a breakthrough in Alzheimer’s disease research that may advance avenues of treatment.
The research lab — led by Kenneth Kosik, co-director of the UCSB Neuroscience Research Institute and professor of neuroscience — has located a protein called BAG2, a site commonly affected in people with Alzheimer’s disease. Alzheimer’s disease is a neurodegenerative illness which causes neurons in the brain to degrade or die, resulting in confusion, dementia, amnesia and eventually death.
BAG2 unravels neurofibrillary tangles — caused by damaged tau proteins, which give the cell structure and transport nutrients — in the brain. When tau proteins are damaged, they begin to clump with other threads, creating tangles that prevent nutrients from moving efficiently and slowly kill the neuron.
Kosik’s team tested BAG2 and discovered that it destroys damaged tau proteins, essentially untangling the neurofibrillary clumps and preventing the degradation of the neuron.
In a press release, Kosik said BAG2 is quite effective at neutralizing these tangles, but may not be present at sufficient concentrations in the case of Alzheimer’s and other related diseases.
“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,” Kosik said. “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.”
According to Kosik, BAG2 can be engineered to only attack damaged tau proteins.
“We’ve done this experiment many ways,” Kosick said, in a press release. “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.”
While the study — published in the February edition of the Journal of Neuroscience — has yet to produce a concrete new treatment for Alzheimer’s, it has provided researchers with a new target for future drugs.
“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,” Kosik said in a press release. “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.”
Thus far, the study has only been conducted in a culture, but the team is set to begin testing the effects of BAG2 in laboratory mice to see how BAG2 functions in a larger biological system.