# LRRK2 and inflammasome pathway in Parkinson's disease

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $607,790

## Abstract

Abstract:
The LRRK2 locus, coding for the LRRK2 (Leucine Rich Repeat Kinase 2) protein, is a major risk factor for
Parkinson’s disease (PD), and mutations in the LRRK2 gene contribute to both genetic and sporadic PD.
Intriguingly, the LRRK2 locus also confers increased risk for Crohn’s disease and leprosy, and LRRK2 is
expressed in immune cells, neurons and glia. We recently discovered that LRRK2 interacts with NOD-like
receptor (NLR) sensor family proteins (NLRPs), NLRP1 and NLRP3. NLRP proteins are key mediators of innate
immunity, and are components of inflammasomes. We propose to test the hypothesis that mutant LRRK2
interacts with and activates the NLRP3- and NLRP1-inflammasomes leading to microglial activation and
neurodegeneration contributing to PD pathology. In Aim 1, we will characterize the interaction of LRRK2 with
NLRP1 and NLRP3 in vitro and in vivo. In Aim 2, we will investigate whether mutant LRRK2 activates the NLRP3-
infammasome in microglial activation, leading to neuroinflammation and degeneration in vitro and in vivo. In
Aim3, we will examine whether mutant LRRK2 activates the NLRP1-inflammsome in neurons, resulting in
neurodegeneration. These studies will elucidate mechanisms underlying LRRK2-linked inflammasome pathway
in neurodegeneration and immune dysfunction. They may also have broader implications for other neurological
diseases related to neuroinflammation. The understanding of NLRP/LRRK2-linked pathways in PD pathogenesis
may reveal potential biomarkers, and may provide novel targets for development of disease-modifying
therapeutic strategies. Thus, this project has the potential for significant impact, and benefits those suffering from
PD and other neurodegenerative diseases.

## Key facts

- **NIH application ID:** 10884198
- **Project number:** 5R01NS119208-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Christopher A Ross
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $607,790
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884198

## Citation

> US National Institutes of Health, RePORTER application 10884198, LRRK2 and inflammasome pathway in Parkinson's disease (5R01NS119208-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10884198. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*