Researchers at this institution are delving into a lesser-known aspect of Parkinson’s disease: the consistent decrease in uric acid levels in patients’ serum and cerebrospinal fluid. Current explanations for this phenomenon are lacking, prompting the need for further research to fully comprehend why this occurs and explore the potential for therapies that could slow down the progression of Parkinson’s disease.
Parkinson’s disease (PD) ranks as the second most common neurodegenerative disorder, and while its exact causes remain unclear, individuals with PD exhibit reduced serum uric acid (UA) levels. Meta-analyses have linked lower UA levels with an increased risk of PD, but the precise relationship between UA levels and PD onset or progression remains uncertain. Research suggests that the decrease in UA levels in PD may not be a direct cause but rather a result of underlying issues like impaired mitochondrial function and altered gastrointestinal and motor functions, which could also impact the development and progression of PD (reverse causation).
Understanding alterations in purine metabolism is vital for grasping why PD patients have lower UA levels. The pathway for UA production involves inosine monophosphate (IMP) → inosine → hypoxanthine → xanthine → UA. While levels of inosine, hypoxanthine, and xanthine may influence UA levels, earlier studies have not explored upstream purine metabolism in the blood and cerebrospinal fluid (CSF) of PD patients.
In this study, we compared levels of inosine, hypoxanthine, xanthine, and UA in the serum and CSF of PD patients and healthy individuals. Using liquid chromatography-tandem mass spectrometry on 132 samples, we found significantly lower UA levels in both serum and CSF of PD patients compared to controls. PD patients also exhibited lower serum hypoxanthine levels and reduced CSF inosine and hypoxanthine levels. These findings suggest that factors beyond purine metabolism, such as sex, weight, and age, may influence decreased UA levels in PD patients. Additionally, reductions in serum and CSF hypoxanthine and CSF inosine hint at potential disruptions in purine recycling pathways, warranting further investigation into alternative therapeutic approaches.
Link: https://doi.org/10.1038/s41531-024-00785-0
