Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson’s disease patients
Authors: Zago Elisa , Dal Molin Alessandra , Dimitri Giovanna Maria , Xumerle Luciano , Pirazzini Chiara , Bacalini Maria Giulia , Maturo Maria Giovanna , Azevedo Tiago , Spasov Simeon , Gómez-Garre Pilar , Periñán María Teresa , Jesús Silvia , Baldelli Luca , Sambati Luisa , Calandra-Buonaura Giovanna , Garagnani Paolo , Provini Federica , Cortelli Pietro , Mir Pablo , Trenkwalder Claudia , Mollenhauer Brit , Franceschi Claudio , Liò Pietro , Nardini Christine ,   PROPAG-AGEING Consortium, Adarmes-Gómez Astrid , Azevedo Tiago , Bacalini Maria Giulia , Baldelli Luca , Bartoletti-Stella Anna , Bhatia Kailash P. , Marta Bonilla-Toribio , Boninsegna Claudia , Broli Marcella , Dolores Buiza-Rueda , Calandra-Buonaura Giovanna , Capellari Sabina , Carrión-Claro Mario , Cilea Rosalia , Clayton Robert , Cortelli Pietro , Molin Alessandra Dal , De Luca Silvia , De Massis Patrizia , Dimitri Giovanna Maria , Doykov Ivan , Escuela-Martin Rocio , Fabbri Giovanni , Franceschi Claudio , Gabellini Anna , Garagnani Paolo , Giuliani Cristina , Gómez-Garre Pilar , Guaraldi Pietro , Hägg Sara , Hällqvist Jenny , Halsband Claire , Heywood Wendy , Houlden Henry , Huertas Ismae , Jesús Silvia , Jylhävä Juulia , Labrador-Espinosa Miguel A. , Licari Cristina , Liò Pietro , Luchinat Claudio , Macias Daniel , Macrì Stefania , Magrinelli Francesca , Rodríguez Juan Francisco Martín , Massimo Delledonne , Maturo Maria Giovanna , Mengozzi Giacomo , Meoni Gaia , Mignani Francesco , Milazzo Maddalena , Mills Kevin , Mir Pablo , Mollenhauer Brit , Nardini Christine , Nassetti Stefania Alessandra , Pedersen Nancy L. , Periñán-Tocino Maria Teresa , Pirazzini Chiara , Provini Federica , Ravaioli Francesco , Sala Claudia , Sambati Luisa , Scaglione Cesa Lorella Maria , Schade Sebastian , Schreglmann Sebastian , Spasov Simeon , Strom Stephen , Tejera-Parrado Cristina , Tenori Leonardo , Trenkwalder Claudia , Turano Paola , Valzania Franco , Ortega Rosario Vigo , Williams Dylan , Xumerle Luciano , Zago Elisa 
Published: January 2022

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.