Compound Helps Combat Parkinson-Linked Protein, According to UA Co-Authored Research in Science

TUSCALOOSA, Ala. — Scientists have identified a chemical compound that enhances cells’ natural abilities to combat a protein linked to Parkinson’s and other neurodegenerative diseases, according to a paper publishing Oct. 24 in the online version of Science and co-authored by University of Alabama researchers.

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, according to the paper. In patients with Parkinson’s, too much alpha-synuclein, previous research has shown, can block the needed movement of proteins within cells and lead to neuron loss.  

“This compound opens up the roadblock,” said Dr. Guy Caldwell, UA professor of biological sciences and one of the paper’s co-authors. It does so, Caldwell said, by serving as an activator of Nedd4, a human protein that manages traffic of other proteins to proper positions with cells.

The research, which was conducted on both worm and yeast model systems, as well as human cells, could, one day, lead to the compound or a related molecule being tested as a potential drug to combat neurodegenerative diseases, like Parkinson’s, Caldwell said.

The collaborative research was led by researchers at the Massachusetts Institute of Technology, along with researchers at UA, Harvard, Purdue and St. Jude’s.

Additional UA co-authors include Dr. Kim Caldwell, professor of biological sciences at UA, and Dr. Michelle Thompson, who earned her doctorate at UA in 2012 and who now holds a post-doctoral research position at The University of Arizona.

A separate companion paper publishing 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, Caldwell 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,” 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.”

The research was funded, in part, by a Howard Hughes Medical Institute Collaborative Innovation grant awarded in 2008.  Through this program, Guy Caldwell joined a five-person team led by Dr. Susan Lindquist, a Howard Hughes Medical Institute investigator. This HHMI-supported team’s goal is to discover new strategies to target the biological mechanisms that break down in Parkinson’s disease and other neurodegenerative disorders.

Lindquist, who led the effort published in Science, is a member and former director of the Whitehead Institute and a professor of biology at MIT.

UA’s department of biological sciences is part of the College of Arts and Sciences, the University’s largest division and the largest liberal arts college in the state. Students from the College have won numerous national awards including Rhodes Scholarships, Goldwater Scholarships, Truman Scholarships and memberships on the USA Today Academic All American Team.


Chris Bryant, UA media relations, 205/348-8323,


Dr. Guy Caldwell, 205/348-9926,