Targeting LRRK2 in Models of Gastrointestinal Inflammation

Study Rationale:
We seek to investigate the extent to which gut inflammation triggers brain inflammation and Parkinson’s-like pathology and the role of LRRK2 and Tumor Necrosis Factor (TNF)-dependent mechanisms in the gut-brain axis, which has been implicated in Parkinson’s pathogenesis.

Hypothesis:
We hypothesize that both LRRK2 and TNF play critical roles in regulating inflammatory responses in the gut-brain connection and that targeting each or both therapeutically may delay or prevent Parkinson’s progression.

Study Design:
We will utilize pre-clinical models of experimental colitis and models of Parkinson’s pathology to investigate the protective effects of various interventions against the effects of gut inflammation on brain inflammation and on the vulnerability of Parkinson’s-relevant brain regions.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
Completion of these studies will provide new critical information on the extent to which gut inflammation triggers brain inflammation and Parkinson’s-like pathology and the role of LRRK2 and TNF-dependent mechanisms in the gut-brain axis.

Next Steps for Development:
Successful completion of these studies may provide mechanism-based rationale to investigate the protective effects of targeting LRRK2- and TNF-dependent inflammation therapeutically in the gut-brain axis in a clinical trial.