Researchers Investigate Nuclear Receptors in Prevention and Treatment of Parkinson Disease


New research from the UH Center for Nuclear Receptors and Cell Signaling (CNRCS) demonstrates that the nuclear receptor liver X receptor β (LXRβ) may play a role in the prevention and treatment of Parkinson Disease. The study, published in Proceedings of the National Academy of Sciences, indicates that the presence of LXRβ promotes the survival of brain cells essential for preventing the progressive neurodegenerative disease.

“The liver X receptor β plays an important role in the development of the central nervous system,” said professor Jan-Åke Gustafsson, whose lab discovered LXRβ. “The receptor continues to show promise as a potential target for the prevention and treatment of Parkinson Disease, as well as other neurological disorders.”

Parkinson Disease is the result of a decrease in dopamine-producing brain cells in the substantia nigra, a section of the midbrain that regulates body control and movement. The disease affects more than 500,000 people in the United States and is theorized to be caused by environmental and/or genetic factors. Prevalence rates increase among people older than 70 years, although the average age of onset ranges from 50-60 years.

To better understand the relationship between LXRβ and the disease, the team of researchers worked with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a chemical which causes Parkinson Disease. They found that the absence of LXRβ increased the harmful effects of MPTP on dopaminergic neurons. Furthermore, an LXR agonist prevented the destructive effects of MPTP and, therefore, may be protective against the neuro-degeneration of the midbrain.

The publication, “Liver X receptor β protects dopaminergic neurons in a mouse model of Parkinson disease,” was authored by CNRCS director Jan-Åke Gustafsson, professor Margaret Warner, research assistant professor Xin-Jie Tan, and postdoctoral fellows Wanfu Wu and Yubing Dai. These latest findings follow another recent LXRβ publication which focused on anxiety and emotional disorders. To view the abstract or full text, visit http://www.pnas.org/content/early/2012/07/18/1210833109.abstract.

Established in 1914, Proceedings of the National Academy of Sciences is among most-cited multidisciplinary scientific research journals and reports on the progressive research of the National Academy of Sciences. The circulation reaches over 3,000 institutions in more than 60 countries, including more than 2,200 Academy members and more than 400 foreign associates.

Established in 2009, CNRCS is a focal point of the UH health initiative. Led by Gustafsson, a world-renowned expert in the field of nuclear receptors, CNRCS researchers are involved in many aspects of nuclear receptor research, all focused on understanding the roles of these receptors in health and disease. CNRCS researchers are working toward the goal of finding new treatments for an array of significant diseases including cancer, diabetes, metabolic syndrome and degenerative neurologic diseases. Working from the Center's world-class labs, CNRCS researchers combine interdisciplinary research and dynamic collaboration with the Texas Medical Center and industry partners.

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