title: Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation.
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.
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France.
authors.forename: Eugénie
authors.initials: E
authors.lastname: Mutez
authors.forename: Lydie
authors.initials: L
authors.lastname: Larvor
authors.forename: Frédéric
authors.initials: F
authors.lastname: Leprêtre
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouroux
authors.forename: Dorota
authors.initials: D
authors.lastname: Hamalek
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kerckaert
authors.forename: Jordi
authors.initials: J
authors.lastname: Pérez-Tur
authors.forename: Nawal
authors.initials: N
authors.lastname: Waucquier
authors.forename: Christel
authors.initials: C
authors.lastname: Vanbesien-Mailliot
authors.forename: Aurélie
authors.initials: A
authors.lastname: Duflot
authors.forename: David
authors.initials: D
authors.lastname: Devos
authors.forename: Luc
authors.initials: L
authors.lastname: Defebvre
authors.forename: Alexandre
authors.initials: A
authors.lastname: Kreisler
authors.forename: Bernard
authors.initials: B
authors.lastname: Frigard
authors.forename: Alain
authors.initials: A
authors.lastname: Destée
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Chartier-Harlin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology*; D025341:Principal Component Analysis; D015398:Signal Transduction / Q000235:genetics; D013223:Statistics as Topic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C113373:LRRN2 protein, human; D014157:Transcription Factors