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
| العنوان: | 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 |
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| المؤلفون: | Janaky Coomaraswamy, Frank Gillardon, Marta Garcia-Miralles, Mathias Jucker, Saskia Biskup, Dagmar Galter, Karina Häbig, Martina Maisel, Natalja Funk, Martin C. Herzig, Thomas Gasser |
| المصدر: | PLoS ONE PLOS ONE 10(4), e0118947 (2015). doi:10.1371/journal.pone.0118947 PLoS ONE, Vol 10, Iss 4, p e0118947 (2015) |
| بيانات النشر: | Public Library of Science, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, pharmacology [Protein Kinase Inhibitors], metabolism [Cytoskeleton], Dopamine, Mutant, lcsh:Medicine, Gene Expression, medicine.disease_cause, Mice, genetics [Parkinson Disease], cytology [Fibroblasts], metabolism [Dopamine], lcsh:Science, antagonists & inhibitors [Protein Serine-Threonine Kinases], Cytoskeleton, Aged, 80 and over, Mutation, Multidisciplinary, Neurodegeneration, metabolism [Neurites], Parkinson Disease, Middle Aged, Protein-Serine-Threonine Kinases, Cell biology, Female, antagonists & inhibitors [Protein-Serine-Threonine Kinases], metabolism [Fibroblasts], Research Article, Genetically modified mouse, Adult, Neurite, drug effects [Neurites], genetics [Protein Serine-Threonine Kinases], Mice, Transgenic, Biology, Protein Serine-Threonine Kinases, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, genetics [Protein-Serine-Threonine Kinases], medicine, Neurites, Animals, Humans, ddc:610, LRRK2 protein, human, Kinase activity, Cell adhesion, Protein Kinase Inhibitors, Aged, drug effects [Fibroblasts], lcsh:R, Wild type, Fibroblasts, medicine.disease, Molecular biology, nervous system diseases, drug effects [Cytoskeleton], lcsh:Q, enzymology [Parkinson Disease] |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c7e6cdd8399aefb612e7e411bdcf9e4Test http://europepmc.org/articles/PMC4382199Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8c7e6cdd8399aefb612e7e411bdcf9e4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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