These findings could provide valuable insight into the development of drug candidates that could protect brain cells in Parkinson’s and other neurodegenerative diseases.
The study, published recently online ahead of print by the journal Molecular and Cellular Biology, focuses on the enzyme known as serum glucocorticoid kinase 1 (SGK1).
“The overexpression of SGK1 provides neuron protection in both cell culture and in animal models,” said Philip LoGrasso, a TSRI professor who led the study. “It decreases reactive oxygen species generation and alleviates mitochondrial dysfunction.”
Using a neurotoxin animal model of neurodegeneration, the study showed that SGK1 protects brain cells by blocking several pathways involved in neurodegeneration, deactivating other molecules known as JNK, GSK3β and MKK4.
Increasing SGK1 offers a potential therapeutic strategy because, as the study makes clear, there isn’t enough naturally occurring SGK1 to do the job.
“Even though the levels of naturally occurring SGK1 increases in the cell under stress, it was not enough to promote cell survival in our neurodegeneration model,” said Sarah Iqbal, the first author of the study and a member of the LoGrasso lab. “On the other hand, cell survival mechanisms tend to dominate when more SGK1 is added to the neurons.”
The LoGrasso lab plans to continue to explore SGK1 as a therapeutic possibility for Parkinson’s disease.
In addition to LoGrasso and Iqbal, other authors of the study, “Serum-Glucocorticoid-Inducible Kinase 1 Confers Protection in Cell-Based and in In Vivo Neurotoxin Models Via the C-Jun N-Terminal Kinase Signaling Pathway,” include Shannon Howard of TSRI. For more information on the study, see http://mcb.asm.org/content/early/2015/03/27/MCB.01510-14.full.pdf
The work was supported by the Department of Defense (grant W81XWH-12-1-0431), the National Institutes of Health (grants U01-NS057153 and GM103825), the Michael J Fox Foundation/23&Me, the Saul and Theresa Esman Foundation and a gift from the McCubbin Family.
About The Scripps Research Institute
The Scripps Research Institute (TSRI) is one of the world’s largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 2,700 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including two Nobel laureates—work toward their next discoveries. The institute’s graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
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