Inflammation is involved in the death of brain cells in Parkinson's disease (PD), but the exact relationship between the two is unclear. We propose that inflammation damages the brain by activating the kynurenine pathway (a series of chemical reactions taking place within the cell). That, in turn, boosts the production of quinolinic acid (QUIN), a known toxin that kills dopamine-producing brain cells. Research studies have linked QUIN production and PD.
We hypothesize that the kynurenine pathway malfunctions in Parkinson's disease, creating excess of QUIN, promoting inflammation and killing dopamine-producing brain cells. In the blood and cerebrospinal fluid, molecules involved the kynurenine pathway may be altered in people with Parkinson's. These changes could be used to distinguish people with PD from healthy individuals.
We will measure molecules involved in the kynurenine pathway as well as inflammation-related molecules in the blood and cerebrospinal fluid of people with PD and in those of healthy people. Collectively, these molecules represent potential biomarkers -- objective measures -- of Parkinson's disease. We will then determine if these biomarkers can indeed be used to diagnose PD and predict how it progresses over time.
Impact on Diagnosis/Treatment of Parkinson's disease:
If our hypothesis is correct, the identified biomarkers will be used to diagnose PD early in its course and to track disease progression. These biomarkers could also be used to determine if new therapies for Parkinson's are effective.
Next Steps for Development:
The next step would be to determine the ability of these biomarkers to correctly identify Parkinson's as opposed to another disease. To accomplish that, we would conduct a large study including individuals with different diagnoses. Also, if the kynurenine pathway does play a role in PD, therapies targeting this pathway could be developed in the future.