Transcriptional profile of Parkinson blood mononuclear cells with LRRK2 mutation.
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.
Mutez
Eugénie
E
Univ Lille Nord de France, F-59000 Lille, France.
Larvor
Lydie
L
Leprêtre
Frédéric
F
Mouroux
Vincent
V
Hamalek
Dorota
D
Kerckaert
Jean-Pierre
JP
Pérez-Tur
Jordi
J
Waucquier
Nawal
N
Vanbesien-Mailliot
Christel
C
Duflot
Aurélie
A
Devos
David
D
Defebvre
Luc
L
Kreisler
Alexandre
A
Frigard
Bernard
B
Destée
Alain
A
Chartier-Harlin
Marie-Christine
MC
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
D015816:Cell Adhesion Molecules, Neuronal; C113373:LRRN2 protein, human; D014157:Transcription Factors