Scripps Research scientists find way to block stress-related cell death

Scientists from the Florida campus of The Scripps Research Institute have uncovered a potentially important new therapeutic target that could prevent stress-related cell death, a characteristic of neurodegenerative diseases such as Parkinson's, as well as heart attack and stroke.

In the study, published recently in the journal ACS Chemical Biology, the scientists showed they could disrupt a specific interaction of a critical enzyme that would prevent cell death without harming other important enzyme functions.

The enzyme in question is c-jun-N-terminal kinase (JNK), pronounced “junk,” which has been implicated in many processes in the body's response to stresses, such as oxidative stress, protein misfolding, and metabolic disorder. JNK also plays an important role in nerve cell survival and has become a target for drugs to treat neurodegenerative disorders such as Parkinson's disease.

In recent studies, JNK has been found to migrate to the mitochondria—the part of the cell that generates chemical energy and that is involved in cell growth and death. That migration, coupled with JNK activation, is associated with a number of serious health issues, including apoptosis or programmed cell death, liver damage, neuronal cell death, stroke and heart attack.

“Activated JNK migrates to the mitochondria in reaction to a stress signal,” said Philip LoGrasso, professor in the Department of Molecular Therapeutics and senior director for drug discovery at Scripps Florida who led the study. “Once there, it amplifies the effects of reactive oxygen species that cause significant damage to the cell. We developed a small peptide that intervenes in JNK migration and blocks those harmful effects—specifically cell death.”

LoGrasso noted that the team was able to block JNK mitochondrial interaction without harming any other important enzyme processes, such as JNK's impact on gene expression. These findings, LoGrasso said, suggest that this interaction could be exploited in the development of a new drug.

“The peptide we developed will never be a drug, but it is an important new investigative tool that we can use to selectively probe mitochondrial biology,” he said. “Our hope is to produce a small molecule that can mimic the inhibitory effect of this peptide. If we can do that, we might be able to selectively inhibit JNK mitochondrial interaction and use it to treat a number of diseases.”

The first author of the study, “Selective Inhibition of Mitochondrial JNK Signaling Achieved Using Peptide Mimicry of the Sab Kinase Interacting Motif-1 (KIM1),” is Jeremy W. Chambers of Scripps Research. Other authors include Lisa Cherry, John D. Laughlin, and Mariana Figuera-Losada, also of Scripps Research. For more information, see http://pubs.acs.org/doi/abs/10.1021/cb200062a .

The study was supported by National Institutes of Health and the Saul and Theresa Esman Foundation.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neuroscience, and vaccine development, as well as for its insights into autoimmune, cardiovascular, and infectious disease. Headquartered in La Jolla, California, the institute also includes a campus in Jupiter, Florida, where scientists focus on drug discovery and technology development in addition to basic biomedical science. Scripps Research currently employs about 3,000 scientists, staff, postdoctoral fellows, and graduate students on its two campuses. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, is ranked among the top ten such programs in the nation.

Media Contact

Mika Ono EurekAlert!

More Information:

http://www.scripps.edu

All latest news from the category: Life Sciences and Chemistry

Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to home

Comments (0)

Write a comment

Newest articles

Lighting up the future

New multidisciplinary research from the University of St Andrews could lead to more efficient televisions, computer screens and lighting. Researchers at the Organic Semiconductor Centre in the School of Physics and…

Researchers crack sugarcane’s complex genetic code

Sweet success: Scientists created a highly accurate reference genome for one of the most important modern crops and found a rare example of how genes confer disease resistance in plants….

Evolution of the most powerful ocean current on Earth

The Antarctic Circumpolar Current plays an important part in global overturning circulation, the exchange of heat and CO2 between the ocean and atmosphere, and the stability of Antarctica’s ice sheets….

Partners & Sponsors