An FDA-approved drug initially used to treat insulin resistance in diabetics has shown promise as a way to improve cognitive performance in some people with Alzheimer's disease.
Working with genetically engineered mice designed to serve as models for Alzheimer's, University of Texas Medical Branch at Galveston researchers found that treatment with the anti-insulin-resistance drug rosiglitazone enhanced learning and memory as well as normalized insulin resistance. The scientists believe that the drug produced the response by reducing the negative influence of Alzheimer's on the behavior of a key brain-signaling molecule.
The molecule, called extracellular signal-regulated kinase (ERK), becomes hyperactive both in the brains of Alzheimer's patients and in the mice at a disease stage corresponding to mild cognitive impairment in human Alzheimer's. This excessive activity leads to improper synaptic transmission between neurons, interfering with learning and memory.
Rosiglitazone brings ERK back into line by activating what's known as the peroxisome proliferator-activated receptor gamma (PPARγ) pathway, which interacts with genes that respond to both PPARγ and ERK.
"Using this drug appears to restore the neuronal signaling required for proper cognitive function," said UTMB professor Larry Denner, the lead author of a paper describing this work now online in the Journal of Neuroscience. "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."
ERK dysfunction in the Alzheimer's mouse model was discovered several years ago by UTMB associate professor Kelly Dineley, senior author of the Journal of Neuroscience paper. But putting together the protein, gene and memory pieces of the puzzle required a multidisciplinary translational research team including 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," Denner said. "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."
Now the UTMB research team and other investigators across the world are starting clinical trials to investigate the value of therapies for insulin resistance in early-stage Alzheimer's disease in humans.
University of Texas Medical Branch at Galveston: http://www.utmb.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Alzheimer's researchers at Harvard for the first time are scanning the brains of healthy patients for the presence of a hallmark protein called tau, which forms toxic tangles of nerve fibers associated with the fatal disease.
Evidence of an ancient settlement was found in the most inaccessible forest in Central America
Strong drugs are rarely warranted to control the behavior of dementia patients, specialists say. But antipsychotic medicine is being overprescribed, and not just among residents of nursing homes.
Scientists are refining what constitutes "normal"
Bumblebees can recall which flowers yield nectar, but like people they can get mixed up – leading them to home in on flowers they have no experience of
Brain cells that help us predict the intentions of others before they've actively made a decision have been discovered in monkeys
Experiments in mice suggest that treatment of haemophilia could be more successful if the baby's immune system is primed while in the womb
Scientists have recovered cultivated wheat DNA from an 8,000-year-old submerged site off the British coast. The finding suggests hunter-gatherers were trading for the grain long before they grew it.
An exciting fossil find in China points to a 525-million year old sea-dweller who used its new backbone to swim nimbly away from predators