This year, as the oldest baby boomers turn 60, scientists are working diligently to understand the aging brain. While scientists have led doctors to recognize and treat symptoms of neurodegenerative diseases—diseases marked by the progressive breakdown of the brain—the causes and prevention of these diseases remain a mystery.
Here at UW-Madison, geneticists are hard at work to help bring scientists one step closer to solving this mystery.
Although the symptoms of many neurodegenerative diseases, like Alzheimer's and Parkinson's Diseases, often afflict patients late in life, researchers believe that chemical changes in the brain occur years before disease symptoms appear. Uncovering the early chemical changes caused by neurodegenerative diseases would help researchers begin to develop earlier detection techniques and preventative drug treatments for future generations.
The symptoms of Parkinson's and Alzheimer's Diseases are caused by disrupted communication between the nerve cells of the brain. In a healthy brain, nerve cells talk through chemical signals, which direct the activities of the body. Much like the signal between cell phones, the stronger the chemical signal, the clearer the message being relayed between nerve cells. In neurodegenerative diseases, clusters of dysfunctional proteins interrupt the message between nerve cells. These clusters decrease the chemical signals between cells (bad service) or cause complete signal interruption (no service). Without the ability to communicate, the cells give up on their failed connections and die.
The breakdown of communication between nerve cells manifests itself through a variety of impaired actions.
Parkinson's Disease leads to labored movement, wavering balance and trembling limbs in its victims; Alzheimer's Disease slowly steals the patient's memory. Both diseases shorten life spans.
Genetic research provides insight into neurodegenerative diseases by helping researchers to understand the abnormal brain function at work, said Dr. Donald Calne, professor of neurology at the University of British Columbia, when speaking at the Parkinson's Disease Public Symposium held recently on campus.
Like detectives on the scene of a crime, geneticists work backwards to make sense of the mess left behind by complex diseases like Alzheimer's and Parkinson's. After gathering evidence about the abnormal activity in brain cells and closely examining a line up of suspected genetic culprits, called mutations, researchers can zero in on the dysfunctional genes to blame for the abnormal activity observed in these diseases.
Under the direction of UW-Madison professor of genetics Barry Ganetzky, graduate student Josh Gnerer uncovered a genetic mutation in a fruit fly that produces changes in behavior and brain activity similar to several symptoms found in human neurodegenerative diseases.
In comparison to healthy flies, the mutant flies showed ""loss of brain tissue, slowed motor skills and a reduced lifespan,"" said Gnerer.
After narrowing in on his genetic suspect, called ""wasted away,"" Gnerer set out to determine how the mutation was causing damage to the nerve cells in the brain.
As it turns out, ""wasted away"" blocked the activity of a protein that assists a basic cellular process. As a result of this blocked protein activity, researchers believe that this mutation leads to the build-up of a toxic compound that causes proteins to dysfunction and accumulate inside the cell.
""Proteins are the work-horses of the cell,"" Ganetzky said. When the work horses are hobbled, cellular functions are disrupted.
Though there are many contributing factors in understanding neurodegenerative diseases, the UW-Madison finding may provide a new model for studying neurodegenerative disorders and the development of therapeutics in the future.
""A lot of information is out there to be uncovered. But now we have developed a good system to study these diseases,"" said Ganetzky. ""Strong evidence suggests that we are on the right track to understanding a contributing factor in neurodegenerative disease.""
