Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson’s disease patients
Elisa Zago, Alessandra Dal Molin, Giovanna Maria Dimitri, Luciano Xumerle, Chiara Pirazzini, Maria Giulia Bacalini, Maria Giovanna Maturo, Tiago Azevedo, S Spasov, Pilar Gómez‐Garre, María Teresa Periñán, Silvia Jesús, Luca Baldelli, Luisa Sambati, Giovanna Calandra–Buonaura, Paolo Garagnani, Federica Provini, Pietro Cortelli, Pablo Mir, Claudia Trenkwalder, Brit Mollenhauer, Claudio Franceschi, Píetro Lió, Christine Nardini, Astrid Adarmes‐Gómez, Tiago Azevedo, Maria Giulia Bacalini, Luca Baldelli, Anna Bartoletti‐Stella, Kailash P. Bhatia, Marta Bonilla‐Toribio, Claudia Boninsegna, Marcella Broli, Dolores Buiza‐Rueda, Giovanna Calandra–Buonaura, Sabina Capellari, Mario Carrión‐Claro, Rosalia Cilea, Robert Clayton, Pietro Cortelli, Alessandra Dal Molin, Silvia De Luca, Patrizia De Massis, Giovanna Maria Dimitri, Ivan Doykov, Rocio Escuela-Martin, Giovanni Fabbri, Claudio Franceschi, A. S. Gabellini, Paolo Garagnani, Cristina Giuliani, Pilar Gómez‐Garre, Pietro Guaraldi, Sara Hägg, Jenny Hällqvist, Claire Halsband, Wendy Heywood, Henry Houlden, Ismae Huertas, Silvia Jesús, Juulia Jylhävä, Miguel A. Labrador‐Espinosa, Cristina Licari, Píetro Lió, Claudio Luchinat, Daniel Macías, S. Macrì, Francesca Magrinelli, Juan Francisco Martín Rodríguez, Delledonne Massimo, Maria Giovanna Maturo, Giacomo Mengozzi, Gaia Meoni, Francesco Mignani, Maddalena Milazzo, Kevin Mills, Pablo Mir, Brit Mollenhauer, Christine Nardini, Stefania Alessandra Nassetti, Nancy L. Pedersen, María Teresa Periñán-Tocino, Chiara Pirazzini, Federica Provini, Francesco Ravaioli, Claudia Sala, Luisa Sambati, Cesa Lorella Maria Scaglione, Sebastian Schade, Sebastian R. Schreglmann, S Spasov, Stephen C. Strom, Cristina Tejera‐Parrado, Leonardo Tenori, Claudia Trenkwalder, Paola Turano, Franco Valzania, Rosario Vigo Ortega, Dylan M. Williams, Luciano Xumerle
Abstract
Advanced age represents one of the major risk factors for Parkinson's Disease. Recent biomedical studies posit a role for microRNAs, also known to be remodelled during ageing. However, the relationship between microRNA remodelling and ageing in Parkinson's Disease, has not been fully elucidated. Therefore, the aim of the present study is to unravel the relevance of microRNAs as biomarkers of Parkinson's Disease within the ageing framework. We employed Next Generation Sequencing to profile serum microRNAs from samples informative for Parkinson's Disease (recently diagnosed, drug-naïve) and healthy ageing (centenarians) plus healthy controls, age-matched with Parkinson's Disease patients. Potential microRNA candidates markers, emerging from the combination of differential expression and network analyses, were further validated in an independent cohort including both drug-naïve and advanced Parkinson's Disease patients, and healthy siblings of Parkinson's Disease patients at higher genetic risk for developing the disease. While we did not find evidences of microRNAs co-regulated in Parkinson's Disease and ageing, we report that hsa-miR-144-3p is consistently down-regulated in early Parkinson's Disease patients. Moreover, interestingly, functional analysis revealed that hsa-miR-144-3p is involved in the regulation of coagulation, a process known to be altered in Parkinson's Disease. Our results consistently show the down-regulation of hsa-mir144-3p in early Parkinson's Disease, robustly confirmed across a variety of analytical and experimental analyses. These promising results ask for further research to unveil the functional details of the involvement of hsa-mir144-3p in Parkinson's Disease.