Evidence map›Paper›PMID 25830304›Full record

ArticlePloS one2015

No dopamine cell loss or changes in cytoskeleton function in transgenic mice expressing physiological levels of wild type or G2019S mutant LRRK2 and in human fibroblasts.

Marta Garcia-Miralles, Janaky Coomaraswamy, Karina Häbig, Martin C Herzig, Natalja Funk, Frank Gillardon, Martina Maisel, Mathias Jucker, Thomas Gasser, Dagmar Galter and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.9field-weighted citation impact, top 10% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  7. Progress inFrontiers in neuroscience · 2020
    Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Robust kinase- and age-dependent dopaminergic and norepinephrine neurodegeneration in LRRK2 G2019S transgenic mice.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  13. Article
  14. Models of LRRK2-Associated Parkinson's Disease.Advances in neurobiology · 2017
    Review
  15. Article
  16. Article
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

11 authors at 5 institutions in 2 countries.

Marta Garcia-MirallesDepartment of Neurodegeneration, Hertie-Institute for Clinical Brain Research and DZNE, German Center for Neurodegenerative Diseases, 72076 Tuebingen, Germany.
Janaky CoomaraswamyDepartment of Cellular Neurology, Hertie-Institute for Clinical Brain Research and DZNE, German Center for Neurodegenerative Diseases, 72076 Tuebingen, Germany.
Karina HäbigDepartment of Medical Genetics and Applied Genomics, Institute of Human Genetics, University of Tuebingen, 72076 Tuebingen, Germany.
Martin C HerzigDepartment of Cellular Neurology, Hertie-Institute for Clinical Brain Research and DZNE, German Center for Neurodegenerative Diseases, 72076 Tuebingen, Germany.
Natalja FunkDepartment of Neurodegeneration, Hertie-Institute for Clinical Brain Research and DZNE, German Center for Neurodegenerative Diseases, 72076 Tuebingen, Germany.
Frank GillardonBoehringer Ingelheim Pharma GmbH & Co. KG, CNS Research, 88397 Biberach an der Riss, Germany.
Martina MaiselDepartment of Neurodegeneration, Hertie-Institute for Clinical Brain Research and DZNE, German Center for Neurodegenerative Diseases, 72076 Tuebingen, Germany.
Mathias JuckerDepartment of Cellular Neurology, Hertie-Institute for Clinical Brain Research and DZNE, German Center for Neurodegenerative Diseases, 72076 Tuebingen, Germany.
Thomas GasserDepartment of Neurodegeneration, Hertie-Institute for Clinical Brain Research and DZNE, German Center for Neurodegenerative Diseases, 72076 Tuebingen, Germany.
Dagmar GalterDepartment of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden.
Saskia BiskupDepartment of Neurodegeneration, Hertie-Institute for Clinical Brain Research and DZNE, German Center for Neurodegenerative Diseases, 72076 Tuebingen, Germany.
Hertie Institute for Clinical Brain Research · DEGerman Center for Neurodegenerative Diseases · DEBoehringer Ingelheim (Germany) · DEKarolinska Institutet · SEUniversity of Tübingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mutations within the LRRK2 gene have been identified in Parkinson's disease (PD) patients and have been implicated in the dysfunction of several cellular pathways. Here, we explore how pathogenic mutations and the inhibition of LRRK2 kinase activity affect cytoskeleton dynamics in mouse and human cell systems. We generated and characterized a novel transgenic mouse model expressing physiological levels of human wild type and G2019S-mutant LRRK2. No neuronal loss or neurodegeneration was detected in midbrain dopamine neurons at the age of 12 months. Postnatal hippocampal neurons derived from transgenic mice showed no alterations in the seven parameters examined concerning neurite outgrowth sampled automatically on several hundred neurons using high content imaging. Treatment with the kinase inhibitor LRRK2-IN-1 resulted in no significant changes in the neurite outgrowth. In human fibroblasts we analyzed whether pathogenic LRRK2 mutations change cytoskeleton functions such as cell adhesion. To this end we compared the adhesion characteristics of human skin fibroblasts derived from six PD patients carrying one of three different pathogenic LRRK2 mutations and from four age-matched control individuals. The mutant LRRK2 variants as well as the inhibition of LRRK2 kinase activity did not reveal any significant cell adhesion differences in cultured fibroblasts. In summary, our results in both human and mouse cell systems suggest that neither the expression of wild type or mutant LRRK2, nor the inhibition of LRRK2 kinase activity affect neurite complexity and cellular adhesion.

Indexed as

MutationAdultAgedAged, 80 and overAnimalsCytoskeletonDopamineFemaleFibroblastsGene ExpressionHumansLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MaleMiceMice, TransgenicMiddle AgedDopamineLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanProtein Kinase InhibitorsProtein Serine-Threonine Kinases

Identifiers

PMID25830304
PMCPMC4382199
OpenAlexW2013846928

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.