Evidence map›Paper›PMID 23560750›Full record

ArticleThe Biochemical journal2013

Comprehensive characterization and optimization of anti-LRRK2 (leucine-rich repeat kinase 2) monoclonal antibodies.

Paul Davies, Kelly M Hinkle, Nour N Sukar, Bryan Sepulveda, Roxana Mesias, Geidy Serrano, Dario R Alessi, Thomas G Beach, Deanna L Benson, Charles L White and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The Biochemical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

64 citing papers in PubMed, 95 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson's disease.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  5. Article
  6. Leucine-rich repeat kinase 2 limits dopamine D1 receptor signaling in striatum and biases against heavy persistent alcohol drinking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Elevated Urinary Rab10 Phosphorylation in Idiopathic Parkinson Disease.Movement disorders : official journal of the Movement Disorder Society · 2022
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
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  20. Article

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 7 institutions in 2 countries.

Paul DaviesMRC Protein Phosphorylation Unit, University of Dundee, Nethergate, Dundee DD1 4HN, Scotland, UK.
Kelly M Hinkle
Nour N Sukar
Bryan Sepulveda
Roxana Mesias
Geidy Serrano
Dario R Alessi
Thomas G Beach
Deanna L Benson
Charles L White
Rita M Cowell
Sonal S Das
Andrew B West
Heather L Melrose
Icahn School of Medicine at Mount Sinai · USUniversity of Alabama at Birmingham · USBanner Sun Health Research Institute · USJacksonville College · USMRC Protein Phosphorylation and Ubiquitylation Unit · GBMichael J. Fox Foundation · USThe University of Texas Southwestern Medical Center · US

Funding

Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI GONZALEZ HERNANDEZ, GRACIELA · 2001 to 2020
$32.5M
ROLE OF GLUTAMATE IN ALZHEIMER'S DISEASEP30AG012300 · NIA · UT SOUTHWESTERN MEDICAL CENTER · PI ROSENBERG, ROGER NEWMAN · 1994 to 2016
$26.6M
National Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8M
Mechanisms of LRRK2 Mediated NeurotoxicityR01NS064934 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI WEST, ANDREW B · 2010 to 2025
$6.3M
Training Program in NeuroscienceT32MH087004 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GEORGE W. HUNTLEY · 2009 to 2026
$4.0M
SYNAPSE TARGETING AND ASSEMBLYR01NS037731 · NINDS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI BENSON, DEANNA L · 1999 to 2010
$2.7M
Functional Characterization of LRRK2 Knock-out and Knock-in Mouse ModelsR01NS065860 · NINDS · MAYO CLINIC JACKSONVILLE · PI MELROSE, HEATHER L · 2010 to 2012
$803k
Role of Sema7A in functional organization of neocortexR01MH095229 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BENSON, DEANNA L, HUNTLEY, GEORGE W. · 2012 to 2013
$790k
Medical Research Council G0700656Medical Research Council MC_G1000735Medical Research Council MC_U127015387Medical Research Council MC_U127070193Medical Research Council MC_UU_12016/2NIA NIH HHS P30 AG012300NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG12300NIA NIH HHS P30 AG19610NIMH NIH HHS R01 MH095229NIMH NIH HHS T32 MH087004NINDS NIH HHS R01 NS064934NINDS NIH HHS R01NS064934NINDS NIH HHS R01NS065860NINDS NIH HHS R01NS37731NINDS NIH HHS U24 NS072026Wellcome Trust 089698
6 · The paper itself

Abstract

Missense mutations in LRRK2 (leucine-rich repeat kinase 2) are a major cause of PD (Parkinson's disease). Several antibodies against LRRK2 have been developed, but results using these polyclonal antibodies have varied widely leading to conflicting conclusions. To address this challenge, the Michael J. Fox Foundation for Parkinson's Research generated a number of monoclonal antibodies targeting epitopes across the LRRK2 protein. In the present paper, we report optimized protocols and results for ten monoclonal antibodies for immunoblotting, immunohistochemistry, immunoprecipitation and kinase activity assays, in rat, mouse and human brain tissue. Several efficacious antibodies were identified, but results demonstrate that the mouse monoclonal N241A/34 is suitable for most applications, with the best overall rabbit monoclonal antibody being c41-2. These antibodies produced a dominant band of the expected size via immunoblotting and a lack of labelling in tissue derived from LRRK2-knockout animals under optimized conditions. A significant proportion of LRRK2 protein localizes to insoluble fractions and no evidence of truncated LRRK2 protein was detected in any fraction from rodent or human tissues. An assay was developed for the robust detection of LRRK2 kinase activity directly from frozen mouse and human brain tissue, but precipitous declines in activity were observed that corresponded to increasing post-mortem intervals and processing times. Finally, we demonstrate the highest levels of brain-localized LRRK2 in the striatum, but note differential expression patterns between rat and mouse in both striatum and cortex. Anti-LRRK2 monoclonal antibodies that are unlimited in availability together with the proposed standardized protocols should aid in the definition of LRRK2 function in both health and disease.

Indexed as

AnimalsAntibodies, MonoclonalBrainCell LineEpitope MappingHumansImmunoblottingLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MaleMiceMice, KnockoutParkinson DiseaseProtein Serine-Threonine KinasesRabbitsRatsAntibodies, MonoclonalLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanLrrk2 protein, mouseLRRK2 protein, ratProtein Serine-Threonine Kinases

Identifiers

PMID23560750
PMCPMC3682752
OpenAlexW1969997447

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.