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New discovery could lead to treatment for Parkinson’s disease

Yulan Xiong, an assistant professor of at UConn Health, and her research team have made a significant breakthrough in the treatment of Parkinson's disease. They have discovered a potential compound that could regulate the disease and bring hope to patients.

Parkinson's disease is often linked to a in the LRRK2 gene, resulting in the excessive production of the daradarin . Until now, scientists struggled to control this protein expression due to a lack of understanding of the underlying mechanisms.

However, the Xiong lab conducted a genome-wide screening and identified an enzyme called ATIC as an LRRK2 regulator at the mRNA level. This was a surprising revelation for the researchers, and it opened new possibilities for treatment.

Further investigations in human neural , fruit fly, and mouse models confirmed that the ATIC enzyme plays a crucial role in regulating LRRK2 levels by influencing purine . Specifically, the ATIC substrate brings in a binding protein called AUF-1 to certain regions of LRRK2 mRNA, which then recruits the DCP1/2 enzyme complex, effectively reducing LRRK2 levels.

To their excitement, Xiong's lab found that AICAr, a drug mimicking ATIC activity, significantly repressed LRRK2 levels in primary neuronal cultures. AICAr had shown promise in preclinical trials for other conditions, but its inability to pass through the blood-brain barrier limited its potential in treating Parkinson's disease.

Undeterred, Xiong and her collaborators are working on modifying AICAr to overcome this challenge. The goal is to find a structure that can penetrate the blood-brain barrier and effectively regulate LRRK2 levels to treat Parkinson's disease successfully.

Xiong and her lab are working closely with UConn's Technology Commercialization Services to protect and leverage their groundbreaking discovery. A non-provisional patent application for the technology has already been filed, and they are connecting with prominent companies specializing in Parkinson's disease treatment to further advance and refine the treatment.

Their plan is to continue conducting animal model trials to gather more data and eventually move towards clinical . If successful, this novel treatment could bring relief and hope to millions of people affected by Parkinson's disease, potentially changing the landscape of Parkinson's treatment for the better.

Source: University of Connecticut

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