Benefits for Albertans
The aging and degenerating brain
Dr. Minh Dang Nguyen looks for ways to protect the nerve cells in our brain from the damage that occurs in normal aging and in such disorders as Alzheimer's disease.
What happens in our brain as we age? This is the question that drives the research of AHFMR Scholar Dr. Minh Dang Nguyen , who arrived at the University of Calgary in September 2005. The main goal in his laboratory is to understand the mechanisms involved in the aging of the brain and in such neurodegenerative disorders as Alzheimer's disease .
One of Dr. Nguyen's research interests is the cytoskeleton, a kind of scaffolding within the nerve cells in the brain (neurons), composed of thread-like structures made of protein. Like any other scaffolding, it provides structure, but it does more than that as well-it transports materials and transmits signals from one part of the cell to another. Changes in the cytoskeleton can lead to such neurodegenerative disorders as Parkinson's disease , amyotrophic lateral sclerosis (also known as ALS, or Lou Gehrig's disease), and Charcot-Marie-Tooth disease -an inherited nerve disorder in which patients slowly lose the use of their limbs as the nerves to the extremities deteriorate.
Dr. Nguyen has recently shifted some of his attention to a gene (called SIRT1) that has been linked to the aging process and disorders related to it. In a lower organism, such as the fruit fly, increasing the number of copies of this gene extends the fly's lifespan, whereas removing the gene shortens it. This gene is somehow linked also to nutrition: researchers have shown that a low-calorie diet extends the lifespan of fruit flies, except that of flies that have reduced numbers of the gene. Research done on primates shows that the presence of this gene may reduce the incidence of age-related disorders such as certain cancers, type 2 diabetes , and neurodegeneration .
This gene, Dr. Nguyen explains, has stress-sensing properties; when it senses conditions that could cause damage to nerve cells, its levels increase to protect the cells. Aging, however, weakens the cell's defensive response to the point where levels of the gene are too low to fight the toxicity. The balance then shifts, and nerves begin to degenerate.
Dr. Nguyen's research team has recently shown that this gene also protects against the neurodegeneration that occurs in models of Alzheimer's disease and ALS. They treated damaged nerve cells with resveratrol -a substance found in the skins of red grapes (and therefore also in red wine) that activates the gene. "We discovered that if you add this compound to neurons that are starting to degenerate, you can actually rescue them," explains Dr. Nguyen. "The neurons not only survive-behaviour tests of treated animals show that [these neurons] are still functional." This discovery could lead to new treatments for both Alzheimer's and ALS.
Because aging is a topic which touches on many other areas of study, Dr. Nguyen has found no shortage of researchers with whom to collaborate. He currently works with AHFMR investigators Dr. Cory Toth and Dr. Douglas Zochodne on nerve regeneration studies, and with Dr. Michael Colicos on synaptic plasticity-a process that regulates the strength of interaction between neurons. The loss of synaptic plasticity is an early sign of Alzheimer's disease. "The environment at the University of Calgary is very collaborative," says Dr. Nguyen. "That is one of the main reasons I came here."