Evidence map›Paper›PMID 29127255›Full record

ArticleThe Biochemical journal2018

Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils.

Ying Fan, Andrew J M Howden, Adil R Sarhan, Pawel Lis, Genta Ito, Terina N Martinez, Kathrin Brockmann, Thomas Gasser, Dario R Alessi, Esther M Sammler

Open access · hybridAbstract read
In one paragraph

Article in The Biochemical journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed
13.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

103 citing papers in PubMed, 176 citations in OpenAlex.

  1. Review
  2. Article
  3. Ex Vivo LRRK2 Activation in Asian G2385R and R1628P Variant Carriers and Idiopathic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  4. Biomarkers of Leucine-Rich Repeat Kinase 2 (LRRK2) and Lysosomal Dysfunction in Progressive Supranuclear Palsy.Movement disorders : official journal of the Movement Disorder Society · 2026
    Article
  5. Large-scale functional annotation establishes a reference framework for humanmedRxiv : the preprint server for health sciences · 2026
    Article
  6. Article
  7. Article
  8. Functional and Structural Characterization of LRRK2 p.V1447L in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2025
    Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Rab10-CAV1 mediated intraluminal vesicle transport to migrasomes.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

43 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Ying FanMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Andrew J M HowdenDivision of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dundee, U.K.
Adil R SarhanMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Pawel LisMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Genta ItoMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K.
Terina N MartinezThe Michael J. Fox Foundation for Parkinson's Research, Grand Central Station, PO Box 4777, New York, NY 10163, U.S.A.
Kathrin BrockmannDepartment of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen 72076, Germany.
Thomas GasserDepartment of Neurodegeneration, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen 72076, Germany.
Dario R AlessiMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K. d.r.alessi@dundee.ac.uk e.m.sammler@dundee.ac.uk.
Esther M SammlerMRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K. d.r.alessi@dundee.ac.uk e.m.sammler@dundee.ac.uk.
Hertie Institute for Clinical Brain Research · DENinewells Hospital · GBUniversity of Dundee · GB

Funding

Medical Research Council G0700656Medical Research Council MC_U127070193Medical Research Council MC_UU_00018/1Medical Research Council MC_UU_12016/2Medical Research Council MR/P00704X/1Parkinson's UK H-1701Parkinson's UK K-1706
6 · The paper itself

Abstract

There is compelling evidence for the role of the leucine-rich repeat kinase 2 (LRRK2) and in particular its kinase function in Parkinson's disease. Orally bioavailable, brain penetrant and potent LRRK2 kinase inhibitors are in the later stages of clinical development. Here, we describe a facile and robust assay to quantify LRRK2 kinase pathway activity by measuring LRRK2-mediated phosphorylation of Rab10 in human peripheral blood neutrophils. We use the selective MJFF-pRab10 monoclonal antibody recognising the Rab10 Thr73 phospho-epitope that is phosphorylated by LRRK2. We highlight the feasibility and practicability of using our assay in the clinical setting by studying a few patients with G2019S LRRK2 associated and sporadic Parkinson's as well as healthy controls. We suggest that peripheral blood neutrophils are a valuable resource for LRRK2 research and should be considered for inclusion in Parkinson's bio-repository collections as they are abundant, homogenous and express relatively high levels of LRRK2 as well as Rab10. In contrast, the widely used peripheral blood mononuclear cells are heterogeneous and only a minority of cells (monocytes and contaminating neutrophils) express LRRK2. While our LRRK2 kinase pathway assay could assist in patient stratification based on LRRK2 kinase activity, we envision that it may find greater utility in pharmacodynamic and target engagement studies in future LRRK2 inhibitor trials.

Indexed as

MutationAnimalsAntibodies, MonoclonalAntibodies, Phospho-SpecificAntibody SpecificityCase-Control StudiesClinical Trials as TopicEnzyme AssaysEpitopesGene Expression RegulationGenetic Predisposition to DiseaseGyrus CinguliHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Leukocytes, MononuclearNeutrophilsAntibodies, MonoclonalAntibodies, Phospho-SpecificEpitopesLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanProtein Kinase InhibitorsRab10 protein, humanrab GTP-Binding Proteinsbiomarkersdiagnosticsleucine-rich repeat kinaseneutrophilsParkinson's diseaseRab10

Identifiers

PMID29127255
PMCPMC5748842
OpenAlexW2767503875

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.