Study Rationale: There is growing interest in the anti-inflammatory properties of cannabis-related compounds as a potential therapy for Parkinson’s disease (PD). Cannabis acts on cannabinoid receptors, including receptor type 2 (CB2). This receptor is thought to be largely responsible for the effect cannabis has on inflammation due to its presence on immune cells found in both the periphery and the brain. Interestingly, levels of CB2 receptors are increased in the PD brain, however the exact role of CB2 in PD is not clear. This project aims to investigate how targeting CB2 alters the behavior of immune cells involved in alpha-synuclein aggregation.
Hypothesis: We hypothesize that by regulating crosstalk between peripheral and central immune cells, the CB2 receptor can alter the inflammatory environment induced by alpha-synuclein.
Study Design: To address this hypothesis, we will expose immune cells called microglia, isolated from the brains of mice, and with mouse forms of alpha-synuclein, a protocol known to promote inflammation. We will then evaluate how treatment with CB2-modulating compounds alter microglial function. We will identify CB2 treatments that promote a wound-healing immune environment and will test them in a preclinical mouse model of PD to determine the effects of CB2 modulation on immune cells that directly interact with alpha-synuclein aggregates.
Impact on Diagnosis/Treatment of Parkinson’s disease: Other labs have demonstrated the trafficking of immune cells from the circulation into the brain in PD. Understanding how CB2 regulates the behavior of immune cells and the conversation between those in the periphery and those that reside in the brain could elucidate new treatments for PD.
Next Steps for Development: If successful, this study will provide evidence for CB2-targeted therapies as a treatment for PD-induced dysfunctional inflammation.