Related Experiment Video
Updated: Nov 7, 2025
Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate
Published on: September 18, 2013
Mind the Gap: LRRK2 Phenotypes in the Clinic vs. in Patient Cells
Liesel Goveas1, Eugénie Mutez1,2, Marie-Christine Chartier-Harlin1
1UMR-S 1172-LilNCog-Lille Neuroscience & Cognition, Université de Lille, Inserm, CHU Lille, F-59000 Lille, France.
Abstract:
Mutations in the Parkinson's disease (PD) protein Leucine Rich Repeat Kinase 2 (LRRK2) have been under study for more than 15 years and our understanding of the cellular phenotypes for the pathogenic mutant forms of LRRK2 has significantly advanced. In parallel to research on LRRK2 mutations in experimental systems, clinical characterization of patients carrying LRRK2 mutations has advanced, as has the analysis of cells that are derived from these patients, including fibroblasts, blood-derived cells, or cells rendered pluripotent. Under the hypothesis that patient clinical phenotypes are a consequence of a cascade of underlying molecular mechanisms gone astray, we currently have a unique opportunity to compare findings from patients and patient-derived cells to ask the question of whether the clinical phenotype of LRRK2 Parkinson's disease and cellular phenotypes of LRRK2 patient-derived cells may be mutually informative. In this review, we aim to summarize the available information on phenotypes of LRRK2 mutations in the clinic, in patient-derived cells, and in experimental models in order to better understand the relationship between the three at the molecular and cellular levels and identify trends and gaps in correlating the data.
Insights
Investigating Leucine Rich Repeat Kinase 2 (LRRK2) mutations in Parkinson's disease (PD) reveals connections between patient phenotypes and cellular behaviors. This review correlates clinical and cellular findings to advance understanding of LRRK2-associated PD.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are a significant genetic factor in Parkinson's disease (PD).
- Over 15 years of research have advanced understanding of cellular phenotypes associated with pathogenic LRRK2 mutations.
- Clinical characterization of patients with LRRK2 mutations and analysis of their derived cells (fibroblasts, blood cells, pluripotent cells) have progressed significantly.
Purpose of the Study:
- To compare clinical phenotypes of LRRK2-associated Parkinson's disease with cellular phenotypes observed in patient-derived cells.
- To explore the hypothesis that clinical manifestations result from a cascade of molecular and cellular dysfunctions.
- To assess whether clinical and cellular findings are mutually informative for understanding LRRK2 Parkinson's disease.
Main Methods:
- Review and synthesis of existing literature on LRRK2 mutations in Parkinson's disease.
- Comparison of data from clinical studies of patients carrying LRRK2 mutations.
- Analysis of cellular phenotypes from patient-derived cells (in vitro) and experimental models.
Main Results:
- Significant advancements in understanding cellular phenotypes of pathogenic LRRK2 mutations.
- Parallel progress in clinical characterization of LRRK2 mutation carriers and their derived cells.
- Identification of an opportunity to correlate clinical and cellular phenotypes for mutual insight.
Conclusions:
- Summarizes available information on LRRK2 mutation phenotypes across clinical, patient-derived cellular, and experimental models.
- Aims to elucidate the relationship between these different levels of observation.
- Identifies trends and knowledge gaps in correlating LRRK2 Parkinson's disease data.
