Validating a novel glycolipid receptor as a disease-modifying therapeutic target for Parkinson’s disease
In Parkinson’s disease (PD) immune cells in the brain, gut and blood become persistently activated due the accumulation of synuclein aggregates and other mechanisms, which can trigger inflammation. Ongoing inflammation is accompanied by changes in the gut microbiome of people with PD. Both these processes have been shown to contribute to the gradual death of dopamine-producing cells in the brain. Therefore, halting the cycle of inflammation, microbiome dysfunction and brain cell death is considered a promising means by which to slow or stop disease progression. Our study will test a new approach by which to accomplish this.
Our research at UQ has uncovered that the levels of a key gut microbiome-sensing receptor are elevated in people with Parkinson’s disease and in animal models. We believe that this signalling pathway could play an important role in regulating persistent inflammation, activation of inflammasomes and early gut dysbiosis in PD.
We will use a combination of studies in PD patient samples, animal models and cultured cells to help us understand the role of this pathway in Parkinson’s disease. We will also test if mice lacking this receptor progress faster or slower in our PD models. These studies will help us to define the role of this new pathway in Parkinson’s disease.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Results from this project will provide us with new insights into the underlying mechanisms involved in Parkinson’s disease. More importantly, these results could provide us with a new approach by which to develop more effective treatments to slow or halt disease progression in people with PD.
Next Steps for Development:
Next steps in this research program include understanding precisely when the changes in this microbiome sensing pathway occur during the disease course in PD. This will allow us to define the best strategy by which this pathway can be targeted as a treatment approach for PD using new or existing drugs.