Researcher identifies key mechanism in Parkinson’s disease

Proper regulation of LRRK2 levels is important for Parkinson’s disease (PD). ATIC, a purine biosynthesis pathway enzyme, and its substrate precursor AICAr regulate LRRK2 mRNA levels via an mRNA decay pathway. AICAr suppresses LRRK2 expression and can rescue LRRK2-induced dopaminergic neurodegeneration and neuroinflammation in PD animal models. Credit: The EMBO Journal (2023). DOI: 10.15252/embj.2022113410

Yulan Xiong, assistant professor of neuroscience at UConn Health, and her team have discovered that a regulator compound holds the potential to treat Parkinson’s disease. Scientists have known that, in most familial cases, Parkinson’s disease is caused by a genetic mutation in a gene called LRRK2. This gene has multiple functions in the brain and other parts of the body including regulating cell function and transmitting signals.

With Parkinson’s disease, mutation to LRRK2 does not cause the protein it codes for, daradarin, to become deformed. Instead, the body begins producing too much of the protein. Until now, scientists did not know how to control this protein expression because they didn’t understand the mechanisms underlying it. The Xiong lab has solved this mystery with their novel study identifying an LRRK2 regulator, an enzyme called ATIC, and a potential pharmaceutical treatment. Xiong recently published these findings in The EMBO Journal. Xiong and her lab first performed a genome-wide screening to identify candidate genes that could be LRRK2 regulators in yeast cells. The ATIC enzyme was regulating LRRK2 at the mRNA level, not at the protein level.

By Anna Zarra Aldrich, University of Connecticut

Article can be accessed on: MedicalXpress