How astrocyte dopamine D2 receptors may drive LRRK2-linked Parkinson's disease
The Role of Striatal Astrocytic Dopamine D2 Receptor Signaling in the Pathogenesis of LRRK2-Mediated Parkinson's Disease
This project looks at whether changes in dopamine D2 receptor signaling in brain support cells (astrocytes) worsen inflammation and early nerve damage in people with LRRK2-related Parkinson’s disease.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Northwestern University NIH-funded |
| Lab location | 1 site (Chicago, United States) |
| Project ID | NIH-11168882 on NIH RePORTER |
What this research studies
Researchers will use mice engineered with the LRRK2 G2019S mutation alongside analyses of donated postmortem brain tissue from people with LRRK2 mutations to study D2 receptor signaling in striatal astrocytes. They will track astrocyte activation, synaptic changes, and inflammatory markers and manipulate D2R and LRRK2 activity to see downstream effects on dopamine neurons. Experiments combine biochemical tests, tissue imaging, and behavioral measures in mice modeling early (prodromal) stages of Parkinson’s disease. The goal is to connect molecular changes in astrocytes to early synaptic inflammation that may contribute to neuron loss in LRRK2-mediated PD.
Who could benefit from this research
Good fit: Findings will be most relevant to people who carry LRRK2 mutations or have family histories of LRRK2-related Parkinson’s disease.
Not a fit: People whose Parkinson’s symptoms are not related to LRRK2 genetic changes or whose disease is driven by non-inflammatory mechanisms may not directly benefit from these findings.
Why it matters
Potential benefit: If successful, this work could reveal new targets to reduce harmful inflammation and help protect dopamine neurons in people with LRRK2-linked Parkinson’s disease.
How similar studies have performed: Prior work shows LRRK2 affects synapses and inflammation and LRRK2 inhibitors are in clinical trials, but directly linking astrocyte D2R signaling to early PD is a novel approach.
Where this research is happening
Chicago, United States
- Northwestern University — Chicago, United States (Active)
Researchers
- Principal investigator: Parisiadou, Loukia — Northwestern University
- Study coordinator: Parisiadou, Loukia
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.