Boosting ubiquitin C-terminal hydrolase L1 (Uch-L1) restores lost memory
By Columbia University Medical Center
Aug 25, 2006, 19:29
Researchers at Columbia University Medical Center have successfully restored normal memory and synaptic function in mice suffering from Alzheimer's disease.
Scientists at Columbia's Taub Institute for Research on Alzheimer's Disease and the Aging Brain have identified an enzyme that is required for normal cognition but that is impaired in a mouse model of Alzheimer's. They discovered that mice regained the ability to form new memories when the enzyme's function was elevated.
The research suggests that boosting the function of this enzyme, known as ubiquitin C-terminal hydrolase L1 (Uch-L1), may provide a promising strategy for battling Alzheimer's disease, and perhaps reversing its effects.
In the new study, the Columbia researchers discovered that the enzyme Uch-L1 is part of a molecular network that controls a memory molecule called CREB, which is inhibited by amyloid beta proteins in people with Alzheimer's. By increasing Uch-L1 levels in mice that had Alzheimer's, they were able to improve the animals' ability to create new memories.
"Because the amyloid beta proteins that cause Alzheimer's may play a normal, important physiological role in the body, we can't destroy them as a therapy," explained Ottavio Arancio, M.D., Ph.D., Assistant Professor of Pathology at Columbia University Medical Center and co-principal investigator of the study with Michael Shelanski, MD, Ph.D., Chairman of the Department of Pathology at the Columbia University College of Physicians and Surgeons. "What makes this newly discovered enzyme exciting as a potentially effective therapy is that it restores memory without destroying amyloid beta proteins."
The researchers tested the memory of the mice by putting them in a cage where they were exposed to a mild stimulus when they touched the cage floor. Mice with normal memory remain still the second time they're placed in the cage, as they recognize the place where they were initially exposed to the stimulus. But mice with Alzheimer's-like changes do not remember the place, and continue moving within the cage. When the Alzheimer's mice were treated with Uch-L1, they acted like normal mice, and remained still.
"While this discovery is very promising, its proven effectiveness is limited to animal models and it will take some time before it could lead to therapies in humans," said Dr. Shelanski. "We continue to work towards that crucial goal." The work was supported by the National Institutes of Neurological Disease and Stroke and the Alzheimer's Center Program of the National Institute of Aging.
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