Evidence map›Paper›PMID 30291536›Full record

ArticleNeurochemical research2019

Differences in Stability, Activity and Mutation Effects Between Human and Mouse Leucine-Rich Repeat Kinase 2.

Rebekah G Langston, Iakov N Rudenko, Ravindran Kumaran, David N Hauser, Alice Kaganovich, Luis Bonet Ponce, Adamantios Mamais, Kelechi Ndukwe, Allissa A Dillman, Amr M Al-Saif and 2 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Neurochemical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.3field-weighted citation impact, top 36% 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

15 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
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  7. Computational modeling of human genetic variants in mice.bioRxiv : the preprint server for biology · 2025
    Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. LRRK2 and Proteostasis in Parkinson's Disease.International journal of molecular sciences · 2022
    Review
  13. Review
  14. Review
  15. LRRK2 links genetic and sporadic Parkinson's disease.Biochemical Society transactions · 2019
    Review
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

12 authors at 1 institution in 1 country.

Rebekah G LangstonLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA.
Iakov N RudenkoLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA.
Ravindran KumaranLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA.
David N HauserLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA.
Alice KaganovichLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA.
Luis Bonet PonceLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA.
Adamantios MamaisLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA.
Kelechi NdukweLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA.
Allissa A DillmanLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA.
Amr M Al-SaifLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA.
Aleksandra BeilinaLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA.
Mark R CooksonLaboratory of Neurogenetics, Cell Biology and Gene Expression Section, NIA, NIH, Bethesda, MD, 20892, USA. cookson@mail.nih.gov.ORCID http://orcid.org/0000-0002-1058-3831
National Institutes of Health · US

Funding

GTPase function of Leucine rich repeat kinase 2ZIAAG000937 · NIA · NATIONAL INSTITUTE ON AGING · PI COOKSON, MARK · 2010 to 2025
$9.2M
Intramural NIH HHS ZIA AG000937NIA NIH HHS Z01AG000937Parkinson's Foundation (US) PF-APDA-SFW-1742
6 · The paper itself

Abstract

Mutations in the Leucine-rich repeat kinase 2 (LRRK2) gene have been implicated in the pathogenesis of Parkinson's disease (PD). Identification of PD-associated LRRK2 mutations has led to the development of novel animal models, primarily in mice. However, the characteristics of human LRRK2 and mouse Lrrk2 protein have not previously been directly compared. Here we show that proteins from different species have different biochemical properties, with the mouse protein being more stable but having significantly lower kinase activity compared to the human orthologue. In examining the effects of PD-associated mutations and risk factors on protein function, we found that conserved substitutions such as G2019S affect human and mouse LRRK2 proteins similarly, but variation around position 2385, which is not fully conserved between humans and mice, induces divergent in vitro behavior. Overall our results indicate that structural differences between human and mouse LRRK2 are likely responsible for the different properties we have observed for these two species of LRRK2 protein. These results have implications for disease modelling of LRRK2 mutations in mice and on the testing of pharmacological therapies in animals.

Indexed as

AnimalsGene Knock-In TechniquesHEK293 CellsHSC70 Heat-Shock ProteinsHSP90 Heat-Shock ProteinsHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MiceMutationPhosphorylationProtein Stabilityrab1 GTP-Binding Proteinsrab GTP-Binding ProteinsHSC70 Heat-Shock ProteinsHSP90 Heat-Shock ProteinsHSPA8 protein, humanLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanLrrk2 protein, mouserab1 GTP-Binding ProteinsRab29 protein, humanrab GTP-Binding ProteinsKinase activityLevel of expressionMouse modelParkinson’s diseaseProtein stability

Identifiers

PMID30291536
PMCPMC6450775
OpenAlexW2895611125

What OpenQuestion holds

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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.