ArticleMolecular & cellular proteomics : MCP2020
Accurate MS-based Rab10 Phosphorylation Stoichiometry Determination as Readout for LRRK2 Activity in Parkinson's Disease.
Article in Molecular & cellular proteomics : MCP, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Omics research in Parkinson's disease: evolution, integrated analysis, pathogenic mechanisms, biomarkers, and therapeutic targets.Frontiers in molecular neuroscience · 2026Pooled it
- LRRK2: Molecular Mechanisms in Parkinson's Disease.International journal of molecular sciences · 2026Review
- The LRRK2 G2019S variant rewires Rab GTPase phosphorylation after lysosomal damage and promotes cell death in human macrophages.Journal of cell science · 2026Article
- Large-scale functional annotation establishes a reference framework for humanmedRxiv : the preprint server for health sciences · 2026Article
- Multi-cohort, cross-species urinary proteomics reveals signatures of LRRK2 dysfunction in Parkinson's disease.Molecular systems biology · 2026Article
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- In-depth mass-spectrometry reveals phospho-RAB12 as a blood biomarker of G2019S LRRK2-driven Parkinson's disease.Brain : a journal of neurology · 2025Article
- PAK6 rescues pathogenic LRRK2-mediated ciliogenesis and centrosomal cohesion defects in a mutation-specific manner.Cell death & disease · 2024Article
- A potential patient stratification biomarker for Parkinson´s disease based on LRRK2 kinase-mediated centrosomal alterations in peripheral blood-derived cells.NPJ Parkinson's disease · 2024Article
- A guide to selecting high-performing antibodies for Rab10 (UniProt ID: P61026) for use in western blot, immunoprecipitation, and immunofluorescence.F1000Research · 2024Article
- Rab29-dependent asymmetrical activation of leucine-rich repeat kinase 2.Science (New York, N.Y.) · 2023Article
- Review
- A leucine-rich repeat kinase 2 (LRRK2) pathway biomarker characterization study in patients with Parkinson's disease with and without LRRK2 mutations and healthy controls.Clinical and translational science · 2023Article
- Insights into the cellular consequences of LRRK2-mediated Rab protein phosphorylation.Biochemical Society transactions · 2023Review
- Middle-Down Mass Spectrometry Reveals Activity-Modifying Phosphorylation Barcode in a Class C G Protein-Coupled Receptor.Journal of the American Chemical Society · 2022Article
- Proteome profiling of cerebrospinal fluid reveals biomarker candidates for Parkinson's disease.Cell reports. Medicine · 2022Article
- Pathogenic LRRK2 regulates centrosome cohesion via Rab10/RILPL1-mediated CDK5RAP2 displacement.iScience · 2022Article
- Distinct profiles of LRRK2 activation and Rab GTPase phosphorylation in clinical samples from different PD cohorts.NPJ Parkinson's disease · 2022Article
- Molecular mechanisms defining penetrance ofMedizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2022Article
- Differential Phospho-Signatures in Blood Cells Identify LRRK2 G2019S Carriers in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Pathogenic mutations in the Leucine-rich repeat kinase 2 (LRRK2) are the predominant genetic cause of Parkinson's disease (PD). They increase its activity, resulting in augmented Rab10-Thr73 phosphorylation and conversely, LRRK2 inhibition decreases pRab10 levels. Currently, there is no assay to quantify pRab10 levels for drug target engagement or patient stratification. To meet this challenge, we developed an high accuracy and sensitivity targeted mass spectrometry (MS)-based assay for determining Rab10-Thr73 phosphorylation stoichiometry in human samples. It uses synthetic stable isotope-labeled (SIL) analogues for both phosphorylated and nonphosphorylated tryptic peptides surrounding Rab10-Thr73 to directly derive the percentage of Rab10 phosphorylation from attomole amounts of the endogenous phosphopeptide. The SIL and the endogenous phosphopeptides are separately admitted into an Orbitrap analyzer with the appropriate injection times. We test the reproducibility of our assay by determining Rab10-Thr73 phosphorylation stoichiometry in neutrophils of LRRK2 mutation carriers before and after LRRK2 inhibition. Compared with healthy controls, the PD predisposing mutation carriers LRRK2 G2019S and VPS35 D620N display 1.9-fold and 3.7-fold increased pRab10 levels, respectively. Our generic MS-based assay further establishes the relevance of pRab10 as a prognostic PD marker and is a powerful tool for determining LRRK2 inhibitor efficacy and for stratifying PD patients for LRRK2 inhibitor treatment.
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Registered trials
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