Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation.
Identifieur interne : 000944 ( PubMed/Corpus ); précédent : 000943; suivant : 000945Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation.
Auteurs : Eugénie Mutez ; Lydie Larvor ; Frédéric Leprêtre ; Vincent Mouroux ; Dorota Hamalek ; Jean-Pierre Kerckaert ; Jordi Pérez-Tur ; Nawal Waucquier ; Christel Vanbesien-Mailliot ; Aurélie Duflot ; David Devos ; Luc Defebvre ; Alexandre Kreisler ; Bernard Frigard ; Alain Destée ; Marie-Christine Chartier-HarlinSource :
- Neurobiology of aging [ 1558-1497 ] ; 2011.
English descriptors
- KwdEn :
- Aged, Aged, 80 and over, Cell Adhesion Molecules, Neuronal (genetics), Female, Gene Expression Profiling (methods), Humans, Leukocytes, Mononuclear (metabolism), Male, Middle Aged, Mutation (genetics), Oligonucleotide Array Sequence Analysis (methods), Parkinson Disease (genetics), Parkinson Disease (pathology), Principal Component Analysis, Signal Transduction (genetics), Statistics as Topic, Transcription Factors (genetics), Transcription Factors (metabolism), Young Adult.
- MESH :
- chemical , genetics : Cell Adhesion Molecules, Neuronal, Transcription Factors.
- genetics : Mutation, Parkinson Disease, Signal Transduction.
- metabolism : Leukocytes, Mononuclear, Transcription Factors.
- methods : Gene Expression Profiling, Oligonucleotide Array Sequence Analysis.
- pathology : Parkinson Disease.
- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Principal Component Analysis, Statistics as Topic, Young Adult.
Abstract
To gain insight into systemic molecular events associated with an age-related neurodegenerative disorder, we compared gene expression patterns in peripheral blood mononuclear cells (PBMCs) sampled from elderly, healthy controls and from Parkinson's disease (PD) patients carrying the most frequently found mutation of the LRRK2 gene (G2019S). A transcriptomic approach enabled us to detect differentially expressed genes and revealed perturbations of pathways known to be involved in PD-related neurodegeneration: the ubiquitin-proteasome system, the mitochondrial oxidation system, inflammation, axonal guidance, calcium signalling and apoptosis. Moreover, alterations of the MAP kinase pathway, the actin cytoskeleton, the ephrin receptor system and vesicular transport - all recently associated with the LRRK2 G2019S mutation pathogenesis - were noted. Furthermore, we acquired new evidences of dysregulation in leukocyte extravasation signalling and immune system pathways in PD. These data show that the G2019S mutation affects the entire body and highlight some of the molecular events observed in the brain. This PBMC transcriptomic approach could be used to better understand neurodegeneration in PD and decipher new pathogenetic mechanisms, even at early stages of the disease.
DOI: 10.1016/j.neurobiolaging.2009.10.016
PubMed: 20096956
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pubmed:20096956Le document en format XML
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<front><div type="abstract" xml:lang="en">To gain insight into systemic molecular events associated with an age-related neurodegenerative disorder, we compared gene expression patterns in peripheral blood mononuclear cells (PBMCs) sampled from elderly, healthy controls and from Parkinson's disease (PD) patients carrying the most frequently found mutation of the LRRK2 gene (G2019S). A transcriptomic approach enabled us to detect differentially expressed genes and revealed perturbations of pathways known to be involved in PD-related neurodegeneration: the ubiquitin-proteasome system, the mitochondrial oxidation system, inflammation, axonal guidance, calcium signalling and apoptosis. Moreover, alterations of the MAP kinase pathway, the actin cytoskeleton, the ephrin receptor system and vesicular transport - all recently associated with the LRRK2 G2019S mutation pathogenesis - were noted. Furthermore, we acquired new evidences of dysregulation in leukocyte extravasation signalling and immune system pathways in PD. These data show that the G2019S mutation affects the entire body and highlight some of the molecular events observed in the brain. This PBMC transcriptomic approach could be used to better understand neurodegeneration in PD and decipher new pathogenetic mechanisms, even at early stages of the disease.</div>
</front>
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<Abstract><AbstractText>To gain insight into systemic molecular events associated with an age-related neurodegenerative disorder, we compared gene expression patterns in peripheral blood mononuclear cells (PBMCs) sampled from elderly, healthy controls and from Parkinson's disease (PD) patients carrying the most frequently found mutation of the LRRK2 gene (G2019S). A transcriptomic approach enabled us to detect differentially expressed genes and revealed perturbations of pathways known to be involved in PD-related neurodegeneration: the ubiquitin-proteasome system, the mitochondrial oxidation system, inflammation, axonal guidance, calcium signalling and apoptosis. Moreover, alterations of the MAP kinase pathway, the actin cytoskeleton, the ephrin receptor system and vesicular transport - all recently associated with the LRRK2 G2019S mutation pathogenesis - were noted. Furthermore, we acquired new evidences of dysregulation in leukocyte extravasation signalling and immune system pathways in PD. These data show that the G2019S mutation affects the entire body and highlight some of the molecular events observed in the brain. This PBMC transcriptomic approach could be used to better understand neurodegeneration in PD and decipher new pathogenetic mechanisms, even at early stages of the disease.</AbstractText>
<CopyrightInformation>Copyright © 2009 Elsevier Inc. All rights reserved.</CopyrightInformation>
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