In the study, published this week in the Journal of Neuroscience, the drug rosiglitazone was used on mice that have been genetically engineered to serve as models for Alzheimer's disease. Researchers found that treatment with the drug improved learning and memory in the mice, while it also normalized insulin resistance.
The researchers believe that the drug reduced the negative influence of Alzheimer's on a brain-signaling molecule called extracellular signal-regulated kinase (ERK). ERK becomes hyperactive in the brains of Alsheimer's patients when they begin to exhibit mild cognitive impairment. This leads to improper synaptic transmission between neurons. The study shows that the drug activates the peroxisome proliferator-activated receptor gamma (PPARy) pathway in the brain, reducing ERK activity.
“Using this drug appears to restore the neuronal signaling required for proper cognitive function,” said Larry Denner, lead author of the study and a University of Texas Medical Branch (UTMB) professor. “It gives us an opportunity to test several FDA-approved drugs to normalize insulin resistance in Alzheimer’s patients and possibly also enhance memory, and it also gives us a remarkable tool to use in animal models to understand the molecular mechanisms that underlie cognitive issues in Alzheimer’s.”
The new research was a joint UTMB effort by animal cognitive neuroscientists, biochemists, molecular biologists, mass spectrometrists, statisticians, and bioinformaticists.
“We were extraordinarily lucky to have this diverse group of experts right here on our campus at UTMB that could coalesce to bring such different ways of thinking to bear on a common problem,” said Denner. “It was quite a challenge to get all of these experts communicating in a common scientific language. But now that we have this team working, we can move on to even more detailed and difficult questions.”