A Model of Simplicity

Albert Einstein said, "Things should be made as simple as possible, but not any simpler."

Paul Weiss, Anne Andrews and colleagues struck the right balance with their model axon, an elegantly simple system that reproduces some of the free-radical damage seen in the brains of people with neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's.

biophysical model of an axon, or nerve fiber, oxidative stress causes the protein cytoskeleton to collapse into a deformed structure resembling a string of beads
Anat Hatzor, Paul Weiss, and Beth Luellen

In chemist Paul Weiss's biophysical model of an axon, or nerve fiber, oxidative stress causes the protein cytoskeleton to collapse into a deformed structure resembling a string of beads (right panel). The center panel shows the same degenerative pattern in actual serotonin neurons in the brain. In the mouse brain (left panel), serotonin axons projecting to the hippocampus-a region involved in learning and memor-are visualized as gold thread-like structures.

Explains Weiss, distinguished professor of chemistry and physics at Penn State, researchers need to be able to model the effects of oxidative stress on neurons (nerve cells) in vitro in order to better comprehend the process that occurs in human beings—in vivo. Previous models had many drawbacks, as scientists had to contend with overly complex systems and undesired interactions.

By contrast, their new system is "very basic—just two lipids, a microtubule protein and a tiny amount of dye." The lipids and protein are the essential features of an axon—the branch-like,communication arm of the neuron. By limiting experiments to the minimal structures required, Weiss hopes to shed new light on complex brain diseases.

"Serendipity" is the word Weiss's colleague, Anne Andrews, uses to describe the model's discovery. "Initially, Paul was purely trying to image the membrane. But when he put a dye on the membranes, he figured out that it generated free radicals that attacked the microtubules."

Weiss adds, "The most important things that my group and I have found have happened when we're looking for one thing and end up seeing another. In this case, we weren't looking for the degradation. This accidental discovery led us to start collaborating with Anne, who is a neuroscientist and had ideas about what we might add to delay or to prevent the degradation we observed. This is our first paper together, and we now have joint students and a couple of joint projects."

"What makes this model so exciting," he concludes, "is that it generates many more questions than it answers. It will allow us to test hypotheses of how damage occurs, and importantly, how we might prevent it. There is a real opportunity to come up with novel therapeutic treatments."

Paul S. Weiss, Ph.D., is distinguished professor of chemistry and physics in the Eberly College of Science; stm@psu.edu.Anne M. Andrews, Ph.D., is assistant professor of molecular toxicology in the College of Agricultural Sciences; ama11@psu.edu.

The project reported above was funded by the National Science Foundation. "A Physical Model of Axonal Damage Due to Oxidative Stress," co-authored by Weiss, Andrews, Anne E. Counterman, and Terrence G. D'Onofrio, was the lead article in the journal, Proceedings
of the National Academy of Sciences of the United States of America (PNAS), on April 4, 2006.

Last Updated April 04, 2006