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Investigating the Potential Role of NOD2 Activation in Reducing a-synuclein Aggregation and Toxicity in Human Cellular and Pre-clinical Models of Parkinson’s Disease

Progress Report

Study Rationale: In Parkinson’s disease (PD), a harmful protein called alpha-synuclein (aSyn) builds up in the brain and other parts of the body. This buildup can damage brain cells and worsen symptoms. A big goal in PD research is finding ways to reduce this protein and protect the brain. Our recent work shows that certain immune cells in the blood can act like "trash collectors" when activated by a signal called NOD2. These cells may help clear out harmful aSyn from the brain and the bloodstream.

Hypothesis: We believe that using special compounds to turn on NOD2 could make these "trash collectors" cells even better at removing aSyn and protecting the brain from damage.

Study Design: In this study, we will first test these compounds on immune cells from people with PD in the lab. Then, we’ll check if these activated “trash cells” can clean up a-syn in human brain cells grown in dishes and in pre-clinical models with PD-like symptoms.

Impact on Diagnosis/Treatment of Parkinson’s disease: This project will show how the immune system can help fight PD and pave the way for a new treatment aimed at stopping, or at least slowing, the progression of the disease.

Next Steps for Development: This project offers a unique bench-to-bedside strategy for PD, with the potential for the compounds we are testing to be used directly in patients to slow or even stop disease progression


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