title: Involvement of the immune system, endocytosis and EIF2 signaling in both genetically determined and sporadic forms of Parkinson's disease.
abstract: 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.
authors.affiliation: UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France; Movement Disorders Department, Neurologic Clinic, University Hospital, Lille, France.
authors.forename: Eugénie
authors.initials: E
authors.lastname: Mutez
authors.affiliation: UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Nkiliza
authors.affiliation: UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Belarbi
authors.affiliation: UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: de Broucker
authors.affiliation: UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Vanbesien-Mailliot
authors.affiliation: UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France; Movement Disorders Department, Neurologic Clinic, University Hospital, Lille, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Bleuse
authors.affiliation: UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Duflot
authors.affiliation: UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Comptdaer
authors.affiliation: UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Semaille
authors.affiliation: Center for Infection and Immunity, Institut Pasteur de Lille, Lille, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Blervaque
authors.affiliation: Center for Infection and Immunity, Institut Pasteur de Lille, Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Hot
authors.affiliation: Functional Genomic Platform, UDSL, IFR114, IRCL, Lille, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Leprêtre
authors.affiliation: Functional Genomic Platform, UDSL, IFR114, IRCL, Lille, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Figeac
authors.affiliation: UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France; Movement Disorders Department, Neurologic Clinic, University Hospital, Lille, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Destée
authors.affiliation: UMR 837 INSERM, Team 6, JPArc, IRCL, Lille, France; Univ Lille Nord de France, Lille, France. Electronic address: marie-christine.chartier-harlin@inserm.fr.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Chartier-Harlin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004705:Endocytosis / Q000235:genetics*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007107:Immune System / Q000503:physiopathology*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D015852:Eukaryotic Initiation Factor-2; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: EIF2 signaling; Endocytosis; Immune response; LRRK2 mutation; PBMC; Parkinson's disease; Peripheral blood mononuclear cell; Transcriptome