Τίτλος:
Circulating Brain-enriched MicroRNAs for detection and discrimination of idiopathic and genetic Parkinson's disease
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: A minimally invasive test for early detection and monitoring of Parkinson's disease (PD) is a highly unmet need for drug development and planning of patient care. Blood plasma represents an attractive source of biomarkers. MicroRNAs (miRNAs) are conserved noncoding RNA molecules that serve as posttranscriptional regulators of gene expression. As opposed to ubiquitously expressed miRNAs that control house-keeping processes, brain-enriched miRNAs regulate diverse aspects of neuron development and function. These include neuron-subtype specification, axonal growth, dendritic morphogenesis, and spine density. Backed by a large number of studies, we now know that the differential expression of neuron-enriched miRNAs leads to brain dysfunction. Objectives: The aim was to identify subsets of brain-enriched miRNAs with diagnostic potential for familial and idiopathic PD as well as specify the molecular pathways deregulated in PD. Methods: Initially, brain-enriched miRNAs were selected based on literature review and validation studies in human tissues. Subsequently, real-time reverse transcription polymerase chain reaction was performed in the plasma of 100 healthy controls and 99 idiopathic and 53 genetic (26 alpha-synucleinA53T and 27 glucocerebrosidase) patients. Statistical and bioinformatics analyses were carried out to pinpoint the diagnostic biomarkers and deregulated pathways, respectively. Results: An explicit molecular fingerprint for each of the 3 PD cohorts was generated. Although the idiopathic PD fingerprint was different from that of genetic PD, the molecular pathways deregulated converged between all PD subtypes. Conclusions: The study provides a group of brain-enriched miRNAs that may be used for the detection and differentiation of PD subtypes. It has also identified the molecular pathways deregulated in PD. © 2019 International Parkinson and Movement Disorder Society. © 2019 International Parkinson and Movement Disorder Society
Συγγραφείς:
Ravanidis, S.
Bougea, A.
Papagiannakis, N.
Maniati, M.
Koros, C.
Simitsi, A.-M.
Bozi, M.
Pachi, I.
Stamelou, M.
Paraskevas, G.P.
Kapaki, E.
Moraitou, M.
Michelakakis, H.
Stefanis, L.
Doxakis, E.
Περιοδικό:
Movement Disorders
Εκδότης:
John Wiley and Sons Inc
Λέξεις-κλειδιά:
microRNA; microRNA 124 3p; microRNA 127 3p; microRNA 128 3p; microRNA 132 3p; microRNA 136 3p; microRNA 139 5p; microRNA 153 3p; microRNA 154 5p; microRNA 22 3p; microRNA 323alpha 3p; microRNA 330 5p; microRNA 338 3p; microRNA 382 5p; microRNA 409 3p; microRNA 410 3p; microRNA 431 3p; microRNA 433 3p; microRNA 485 5p; microRNA 495 3p; microRNA 7 5p; unclassified drug; alpha synuclein; circulating microRNA; microRNA, adult; aged; Article; bioinformatics; cohort analysis; controlled study; female; Gaucher disease; human; human tissue; idiopathic disease; major clinical study; male; molecular fingerprinting; molecular pathology; Parkinson disease; priority journal; real time reverse transcription polymerase chain reaction; synucleinopathy; brain; genetics; metabolism, alpha-Synuclein; Brain; Circulating MicroRNA; Humans; MicroRNAs; Parkinson Disease
