Role of the JAK/STAT Pathway in Parkinson's Disease

Promising Outcomes of Original Grant:
We aim to determine if hyperactivation of the JAK/STAT (cellular signaling) pathway is involved in Parkinson's disease pathology. Using a pre-clinical model of PD, we found that pharmacologic inhibition of the JAK/STAT pathway prevented both neuroinflammatory and neurodegenerative responses in the alpha-synuclein model of PD. Our hypothesis was verified by our experimental findings.

Objectives for Supplemental Investigation:
We will investigate the JAK/STAT pathway by studying immune cells obtained from individuals with PD and healthy controls. Our hypothesis is that monocytes and T-cells (immune system cells) from PD patients will exhibit heightened activation of the JAK/STAT pathway and gene expression compared to controls. This work will establish whether the JAK/STAT pathway is a valid therapeutic target.

Importance of This Research for the Development of a New PD Therapy:
Several JAK inhibitors (medications that decrease activity of certain enzymes) are FDA-approved and may serve as new therapeutic agents for PD patients. JAK inhibitors may reduce the inflammatory response associated with PD, potentially in both the periphery and central nervous system, which may slow the neurodegenerative process. These small molecule inhibitors have a good safety profile, furthering the premise for their clinical application in PD.