Alice Serafin1, Luisa Foco1, Stefano Zanigni1, Hagen Blankenburg1, Anne Picard1, Alessandra Zanon1, Giulia Giannini1, Irene Pichler1, Maurizio F Facheris1, Pietro Cortelli1, Peter P Pramstaller1, Andrew A Hicks1, Francisco S Domingues1, Christine Schwienbacher2. 1. From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany. 2. From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany. christine.schwienbacher@eurac.edu.
Abstract
OBJECTIVE: The aims of the present study were to profile the expression of several candidate microRNAs (miRNAs) in blood from L-dopa-treated and drug-naive patients with Parkinson disease (PD) vs unaffected controls and to interpret the miRNA expression data in a biological context. METHODS: We analyzed RNAs from peripheral blood of 36 L-dopa-treated, 10 drug-naive patients with PD and unaffected controls matched 1:1 by sex and age. We evaluated expression by reverse transcription-quantitative real-time PCR, and we analyzed data using a 2-tailed paired t test. To detect miRNA targets, several miRNA resources were combined to generate an overall score for each candidate gene using weighted rank aggregation. RESULTS: Significant overexpression of miR-103a-3p (p < 0.0001), miR-30b-5p (p = 0.002), and miR-29a-3p (p = 0.005) in treated patients with PD was observed, and promising candidate target genes for these were revealed by an integrated in silico analysis. CONCLUSIONS: We revealed 3 candidate biomarkers for PD. miRNAs 30b-5p and 29a-3p replicated a documented deregulation in PD albeit opposite to published data, while for miR-103a-3p, we demonstrated for the first time an overexpression in treated patients with PD. Expression studies in patients and/or in isolated peripheral blood mononuclear cells before and after L-dopa administration are necessary to define the involvement of L-dopa treatment in the observed overexpression. Our in silico analysis to prioritize targets of deregulated miRNAs identified candidate target genes, including genes related to neurodegeneration and PD. Despite the preliminary character of our study, the results provide a rationale for further clarifying the role of the identified miRNAs in the pathogenesis of PD and for validating their diagnostic potential.
OBJECTIVE: The aims of the present study were to profile the expression of several candidate microRNAs (miRNAs) in blood from L-dopa-treated and drug-naive patients with Parkinson disease (PD) vs unaffected controls and to interpret the miRNA expression data in a biological context. METHODS: We analyzed RNAs from peripheral blood of 36 L-dopa-treated, 10 drug-naive patients with PD and unaffected controls matched 1:1 by sex and age. We evaluated expression by reverse transcription-quantitative real-time PCR, and we analyzed data using a 2-tailed paired t test. To detect miRNA targets, several miRNA resources were combined to generate an overall score for each candidate gene using weighted rank aggregation. RESULTS: Significant overexpression of miR-103a-3p (p < 0.0001), miR-30b-5p (p = 0.002), and miR-29a-3p (p = 0.005) in treated patients with PD was observed, and promising candidate target genes for these were revealed by an integrated in silico analysis. CONCLUSIONS: We revealed 3 candidate biomarkers for PD. miRNAs 30b-5p and 29a-3p replicated a documented deregulation in PD albeit opposite to published data, while for miR-103a-3p, we demonstrated for the first time an overexpression in treated patients with PD. Expression studies in patients and/or in isolated peripheral blood mononuclear cells before and after L-dopa administration are necessary to define the involvement of L-dopa treatment in the observed overexpression. Our in silico analysis to prioritize targets of deregulated miRNAs identified candidate target genes, including genes related to neurodegeneration and PD. Despite the preliminary character of our study, the results provide a rationale for further clarifying the role of the identified miRNAs in the pathogenesis of PD and for validating their diagnostic potential.
Authors: Alexander G Thompson; Elizabeth Gray; Sabrina M Heman-Ackah; Imre Mäger; Kevin Talbot; Samir El Andaloussi; Matthew J Wood; Martin R Turner Journal: Nat Rev Neurol Date: 2016-05-13 Impact factor: 42.937