A groundbreaking discovery has been made by a scientist from the University of Connecticut in the field of Parkinson’s disease research. Yulan Xiong, an assistant professor of neuroscience at UConn Health, and her team have identified a regulator compound that shows great potential in treating this brain disorder. The research, which focused on the gene LRRK2, was recently published in The EMBO Journal.
According to the university, Parkinson’s disease is often caused by a genetic mutation in the LRRK2 gene in familial cases. This gene plays multiple roles in the brain. However, until now, scientists did not fully understand the mechanism behind the overproduction of the protein daradarin, which is coded by the LRRK2 gene.
The team, led by Xiong and PhD student Qinfang Liu, identified the regulator of LRRK2 as an enzyme called ATIC and discovered a potential pharmaceutical treatment. The laboratory conducted a genome-wide screening to identify candidate genes that could regulate LRRK2 in yeast cells. Ultimately, they found that the enzyme regulated the gene at the Messenger RNA (mRNA) level, which is the genetic material responsible for protein synthesis.
To further validate their findings, the researchers examined the enzyme in human neural cells, as well as in fruit fly and mouse models. They observed that the ATIC substrate, which recruits a binding protein called AUF-1 to specific regions of LRRK2 mRNA, significantly reduced LRRK2 levels. Additionally, they discovered that AICAr, a drug that mimics ATIC activity, successfully suppressed LRRK2 levels.
Xiong emphasized the significance of their study, stating, “Our study is the first to uncover the mechanism behind LRRK2 regulation. It’s also important that we identified a compound that can directly decrease LRRK2 levels, offering potential treatment options for Parkinson’s patients.”
AICAr has shown promise in preclinical trials for treating other conditions; however, its inability to cross the blood-brain barrier has been a challenge. Xiong and her team are currently working to overcome this obstacle.
Recognizing the potential of this research, UConn’s Technology Commercialization Services has filed a non-provisional patent application for the technology. They are also facilitating connections between Xiong and leading companies specializing in Parkinson’s disease treatment.
With the number of people living with Parkinson’s disease projected to rise to 1.2 million in the U.S. by 2030, the significance of this discovery cannot be understated. The Parkinson’s Foundation reports that nearly 90,000 U.S. individuals are diagnosed with Parkinson’s disease each year, with men being 1.5 times more likely to develop the condition than women.
As this groundbreaking research continues to progress, it offers hope for the development of new treatments and improved quality of life for individuals affected by Parkinson’s disease.
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