Researchers have found that individuals with Parkinson’s disease display decreased levels of uric acid and issues with energy recycling. This challenges earlier notions regarding the significance of uric acid in the disease. Such findings could pave the way for innovative treatments targeting energy metabolism.
Parkinson’s disease (PD) stands as the second most prevalent neurodegenerative disorder worldwide, leaving researchers puzzled due to its progressive characteristic and severe impact on motor abilities.
A recent investigation by the School of Medicine at Fujita Health University has provided fresh perspectives on the metabolic irregularities that patients with PD experience. By examining the blood and cerebrospinal fluid (CSF) of these individuals, scientists discovered important flaws in purine metabolism and the recycling of adenosine triphosphate (ATP)—the key molecule that powers cellular energy.
For a long time, researchers have observed that PD patients tend to have lower levels of uric acid. Uric acid, known for its antioxidant effects, was previously thought to have a direct impact on the illness by mitigating oxidative stress in the brain. However, this study, published in NPJ Parkinson’s Disease on September 9, 2024, shows that the reality is more intricate.
Lead author Dr. Watanabe commented, “Our results indicate that the decrease in uric acid levels among PD patients is influenced by more factors than just purine metabolism, including external variables like gender, weight, and age.” This finding implies that the connection between uric acid and PD is far more complicated than assumed and involves more than mere oxidative stress.
Using targeted metabolomics to evaluate purine metabolites such as inosine, hypoxanthine, xanthine, and uric acid, researchers found that PD patients had notably lower levels of uric acid in both serum and CSF when compared to healthy individuals. They also noted a decrease in hypoxanthine levels, another purine metabolite.
The research indicated that the drops in serum and CSF uric acid were associated with body weight and sex, but not with the upstream metabolite xanthine, contradicting previous beliefs about purine metabolism. Dr. Watanabe elaborated, “Our research shows that uric acid levels in serum and CSF do not have a direct correlation with xanthine levels, suggesting there are other influences at play beyond traditional purine metabolism pathways.”
This finding is significant because it highlights a dysfunction in the ATP recycling mechanism. ATP is crucial for energy usage in cells, and its effective breakdown and recycling are essential for maintaining optimal cell performance. In PD, this process appears to be impaired, creating an energy shortfall that might worsen the symptoms of the disease.
Another aspect of the study focused on inosine, the precursor to uric acid. The researchers noticed a significant reduction of inosine in the CSF of PD patients, whereas serum levels showed no such decline. Dr. Watanabe stated, “The significant drop in CSF inosine may suggest a reduction in nucleotide production within the central nervous system, which could have serious ramifications for energy generation in the brain.”
The study also revealed that, relative to healthy controls, patients with PD had significantly lower levels of hypoxanthine in both serum and CSF. Notably, more than 90% of hypoxanthine is converted back into inosine monophosphate (IMP) in the salvage pathway, playing a vital role in sustaining energy production.
The revelation that energy metabolism is compromised in PD opens up new avenues for treatment strategies. Current therapies are primarily about alleviating symptoms, but this research indicates that enhancing the body’s energy recycling could help slow disease progression. The study suggests that treatments designed to increase uric acid levels may not be very effective in treating Parkinsonism. Rather, boosting the purine recycling mechanism, particularly enhancing ATP production, could be a more promising approach.
As the research moves forward, the team intends to investigate exercise and nutritional strategies as potential methods to enhance energy metabolism and ATP recycling.
In summary, this groundbreaking research brings us closer to comprehending the intricate metabolic changes associated with PD. By focusing on energy metabolism and the purine recycling system, scientists could develop novel treatments that not only impede the disease’s progress but also enhance the quality of life for those affected by it.
