Περίληψη:
Objective: There is a pressing need to identify and validate, minimally invasive, molecular biomarkers that will complement current practices and increase the diagnostic accuracy in Parkinson’s disease (PD). Brain-enriched miRNAs regulate all aspects of neuron development and function; importantly, they are secreted by neurons in amounts that can be readily detected in the plasma. Τhe aim of the present study was to validate a set of previously identified brain-enriched miRNAs with diagnostic potential for idiopathic PD and recognize the molecular pathways affected by these deregulated miRNAs. Methods: RT-qPCR was performed in the plasma of 92 healthy controls and 108 idiopathic PD subjects. Statistical and in silico analyses were used to validate deregulated miRNAs and pathways in PD, respectively. Results: miR-22-3p, miR-124-3p, miR-136-3p, miR-154-5p, and miR-323a-3p levels were found to be differentially expressed between healthy controls and PD patients. miR-330-5p, miR-433-3p, and miR-495-3p levels were overall higher in male subjects. Most of these miRNAs are clustered at Chr14q32 displaying CREB1, CEBPB, and MAZ transcription factor binding sites. Gene Ontology annotation analysis of deregulated miRNA targets revealed that “Protein modification,” “Transcription factor activity,” and “Cell death” terms were over-represented. Kyoto Encyclopedia of Genes and Genome analysis revealed that “Long-term depression,” “TGF-beta signaling,” and “FoxO signaling” pathways were significantly affected. Interpretation: We validated a panel of brain-enriched miRNAs that can be used along with other measures for the detection of PD, revealed molecular pathways targeted by these deregulated miRNAs, and identified upstream transcription factors that may be directly implicated in PD pathogenesis. © 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
Συγγραφείς:
Ravanidis, S.
Bougea, A.
Papagiannakis, N.
Koros, C.
Simitsi, A.M.
Pachi, I.
Breza, M.
Stefanis, L.
Doxakis, E.
Λέξεις-κλειδιά:
CREB1 gene; microRNA; microRNA 124 3p; microRNA 136 3p; microRNA 154 5p; microRNA 22 3p; microRNA 323a 3p; transcription factor; unclassified drug; biological marker; microRNA, adult; Article; cell death; chromosome; computer model; controlled study; CREB1 gene; discriminant analysis; female; gene; gene ontology; human; long term depression; major clinical study; male; nerve cell differentiation; Parkinson disease; plasma; priority journal; protein modification; real time polymerase chain reaction; signal transduction; aged; blood; metabolism; middle aged; Parkinson disease; pathophysiology, Aged; Biomarkers; Female; Humans; Male; MicroRNAs; Middle Aged; Parkinson Disease
