Targeting the NLRP3 Inflammasome in Models of Parkinson's Disease
Target Validation, 2015
Objective/Rationale: † † † † † ††
Chronic inflammation within the brain is emerging as a possible driver in the progression of Parkinsonís 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.
We will initially characterize the expression of key components of this inflammasome complex in Parkinsonís brain samples. In parallel, we will also confirm expression and activation of this inflammasome pathway in two pre-clinical models of Parkinsonís 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 Parkinsonís Disease: † † † † † † † † † ††
Our findings will directly implicate the inflammasome in the progression of Parkinsonís 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 Parkinsonís 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 Parkinsonís disease. Ultimately, this may accelerate new therapeutics into clinical trials for the treatment of Parkinsonís disease.
Associate Professor of Pharmacology and NHMRC RD Wright Biomedical Fellow at The University of Queensland
Location: Brisbane, Queensland, Australia