Objective/Rationale:
Chronic inflammation within the brain is emerging as a possible driver in the progression of Parkinson’s disease (PD). Inflammasomes are protein complexes that function as sensors of cell stress and abnormal proteins, which drive inflammatory responses. This project aims to identify the contribution of the inflammasome in PD pathology and to ascertain the therapeutic potential of a novel inflammasome inhibitory drug developed by our research team.
Project Description:
We will initially characterize the expression of key components of this inflammasome complex in Parkinson’s brain samples. In parallel, we will also confirm expression and activation of this inflammasome pathway in two pre-clinical models of Parkinson’s disease. Finally, we will test a novel inflammasome inhibitory drug in PD models to test if blocking this inflammation cycle can reduce brain cell death and halt disease progression.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Our findings will directly implicate the inflammasome in the progression of Parkinson’s disease. If true, this will open the possibility of targeting the inflammasome with novel drugs in order to slow or halt disease progression.
Anticipated Outcome:
We expect to find that the inflammasome is primed and activated in Parkinson’s disease, which will identify a new therapeutic approach to treat this disease. We anticipate that by inhibiting inflammasome activation with a novel, orally active and brain-permeable drug developed by our group, we can reduce disease burden in preclinical models of Parkinson’s disease. Ultimately, this may accelerate new therapeutics into clinical trials for the treatment of Parkinson’s disease.