College News

Caldwell Lab Collaborates on Groundbreaking Research

From the November 2013 Desktop News Scientists have identified a chemical compound that enhances cells’ natural abilities to combat a protein linked to Parkinson’s and other neurodegenerative diseases. The findings, which were recently published in Science online, could lead to the compound or a related molecule being tested as a potential drug to combat these diseases.

Drs. Guy and Kim Caldwell, both professors in the Department of Biological Sciences, collaborated with researchers at the Massachusetts Institute of Technology, Harvard University, Purdue University, and St. Jude’s Children’s Research Hospital on the findings. They were also assisted by Dr. Michelle Thompson, a 2012 UA graduate who now holds a post-doctoral research position at The University of Arizona.

They found that the compound, N-aryl benzimidazole, or NAB, promotes the work that one of the body’s naturally occurring proteins does in attempts to overcome the toxic effects of alpha-synuclein, a human protein found in the brain. Previous research has shown that in patients with Parkinson’s, too much alpha-synuclein can block the needed movement of proteins within cells and lead to neuron loss.

According to Guy Caldwell, the compound acts as a way to open the roadblock caused by too much alpha-synuclein. It does so by serving as an activator of Nedd4, a human protein that manages traffic of other proteins to proper positions with cells.

A separate companion paper published in the same issue of Science demonstrates that NAB can also enhance survival of human cells derived using a Nobel Prize-winning technique known as iPS, he said.

iPS cells, shown to be an alternative to the controversial embryonic stem cell transplants, are derived by a method in which researchers can take healthy skin cells from a diseased patient, reprogram them back to their embryonic state and then regenerate them into a different cell type, such as neurons, needed by the patient.

As in this study, iPS regenerated cells can be used in evaluation and validation of new therapeutics, but they may eventually be transplanted back into the body as well.

“It’s very rewarding,” Guy Caldwell said, “to see how the basic science that is revealed through working on a simple system like yeast, or worms, can rapidly accelerate the discovery of drugs that are showing impact on human cells.”