Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease
The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is a common genetic cause of Parkinson's disease (PD). Although patients with sporadic PD and individuals with LRRK2-linked PD display the classical PD phenotype, it is not known whether or not the same biological pathways are deregulated...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-03-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996113003197 |
| _version_ | 1819159860417134592 |
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| author | Eugénie Mutez Aurore Nkiliza Karim Belarbi Amélie de Broucker Christel Vanbesien-Mailliot Séverine Bleuse Aurélie Duflot Thomas Comptdaer Pierre Semaille Renaud Blervaque David Hot Frederic Leprêtre Martin Figeac Alain Destée Marie-Christine Chartier-Harlin |
| author_facet | Eugénie Mutez Aurore Nkiliza Karim Belarbi Amélie de Broucker Christel Vanbesien-Mailliot Séverine Bleuse Aurélie Duflot Thomas Comptdaer Pierre Semaille Renaud Blervaque David Hot Frederic Leprêtre Martin Figeac Alain Destée Marie-Christine Chartier-Harlin |
| author_sort | Eugénie Mutez |
| collection | DOAJ |
| description | The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is a common genetic cause of Parkinson's disease (PD). Although patients with sporadic PD and individuals with LRRK2-linked PD display the classical PD phenotype, it is not known whether or not the same biological pathways are deregulated in each context. By using transcriptome profiling, we investigated the deregulation of various biological pathways in a total of 47 peripheral blood mononuclear cell (PBMC) samples from patients with sporadic PD, patients heterozygous for the LRRK2 G2019S mutation compared to healthy controls. We found that the deregulation patterns were indeed similar in PBMCs obtained from patients with sporadic PD and from LRRK2 G2019S carriers, with dysfunctions in mitochondrial pathways, cell survival signaling, cancerization, endocytosis signaling and iron metabolism. Analysis of our PBMC data and other publicly available transcriptome datasets (for whole blood samples) showed that deregulation of the immune system, endocytosis and eukaryotic initiation factor 2 (EIF2) signaling are the main features of transcriptome profiles in PD (since they are also present in the transcriptome of dopaminergic neurons from patients). Transcriptome analysis of PBMCs is thus valuable for (i) characterizing the pathophysiological pathways shared by genetic and sporadic forms of PD and (ii) identifying potential biomarkers and therapeutic targets. This minimally invasive approach opens up tremendous perspectives for better diagnosis and therapy of neurodegenerative diseases because it can be applied from the earliest stages of the disease onwards. |
| first_indexed | 2024-12-22T16:47:16Z |
| format | Article |
| id | doaj.art-af4a7a6f76bc4933b843c3785a6a421f |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-22T16:47:16Z |
| publishDate | 2014-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-af4a7a6f76bc4933b843c3785a6a421f2022-12-21T18:19:42ZengElsevierNeurobiology of Disease1095-953X2014-03-0163165170Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's diseaseEugénie Mutez0Aurore Nkiliza1Karim Belarbi2Amélie de Broucker3Christel Vanbesien-Mailliot4Séverine Bleuse5Aurélie Duflot6Thomas Comptdaer7Pierre Semaille8Renaud Blervaque9David Hot10Frederic Leprêtre11Martin Figeac12Alain Destée13Marie-Christine Chartier-Harlin14UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France; Movement Disorders Department, Neurologic Clinic, University Hospital, Lille, FranceUMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, FranceUMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, FranceUMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, FranceUMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, FranceUMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France; Movement Disorders Department, Neurologic Clinic, University Hospital, Lille, FranceUMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, FranceUMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, FranceUMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, FranceCenter for Infection and Immunity, Institut Pasteur de Lille, Lille, FranceCenter for Infection and Immunity, Institut Pasteur de Lille, Lille, FranceFunctional Genomic Platform, UDSL, IFR114, IRCL, Lille, FranceFunctional Genomic Platform, UDSL, IFR114, IRCL, Lille, FranceUMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France; Movement Disorders Department, Neurologic Clinic, University Hospital, Lille, FranceUMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France; Corresponding author at: UMR 837 INSERM, Team 6, JPArc, IRCL, Place de Verdun, F-59045 Lille cedex, France. Fax: +33 320 169 229.The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is a common genetic cause of Parkinson's disease (PD). Although patients with sporadic PD and individuals with LRRK2-linked PD display the classical PD phenotype, it is not known whether or not the same biological pathways are deregulated in each context. By using transcriptome profiling, we investigated the deregulation of various biological pathways in a total of 47 peripheral blood mononuclear cell (PBMC) samples from patients with sporadic PD, patients heterozygous for the LRRK2 G2019S mutation compared to healthy controls. We found that the deregulation patterns were indeed similar in PBMCs obtained from patients with sporadic PD and from LRRK2 G2019S carriers, with dysfunctions in mitochondrial pathways, cell survival signaling, cancerization, endocytosis signaling and iron metabolism. Analysis of our PBMC data and other publicly available transcriptome datasets (for whole blood samples) showed that deregulation of the immune system, endocytosis and eukaryotic initiation factor 2 (EIF2) signaling are the main features of transcriptome profiles in PD (since they are also present in the transcriptome of dopaminergic neurons from patients). Transcriptome analysis of PBMCs is thus valuable for (i) characterizing the pathophysiological pathways shared by genetic and sporadic forms of PD and (ii) identifying potential biomarkers and therapeutic targets. This minimally invasive approach opens up tremendous perspectives for better diagnosis and therapy of neurodegenerative diseases because it can be applied from the earliest stages of the disease onwards.http://www.sciencedirect.com/science/article/pii/S0969996113003197Parkinson's diseaseTranscriptomePeripheral blood mononuclear cellPBMCLRRK2 mutationImmune response |
| spellingShingle | Eugénie Mutez Aurore Nkiliza Karim Belarbi Amélie de Broucker Christel Vanbesien-Mailliot Séverine Bleuse Aurélie Duflot Thomas Comptdaer Pierre Semaille Renaud Blervaque David Hot Frederic Leprêtre Martin Figeac Alain Destée Marie-Christine Chartier-Harlin Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease Neurobiology of Disease Parkinson's disease Transcriptome Peripheral blood mononuclear cell PBMC LRRK2 mutation Immune response |
| title | Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease |
| title_full | Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease |
| title_fullStr | Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease |
| title_full_unstemmed | Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease |
| title_short | Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease |
| title_sort | involvement of the immune system endocytosis and eif2 signaling in both genetically determined and sporadic forms of parkinson s disease |
| topic | Parkinson's disease Transcriptome Peripheral blood mononuclear cell PBMC LRRK2 mutation Immune response |
| url | http://www.sciencedirect.com/science/article/pii/S0969996113003197 |
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