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1. Metabolite and lipoprotein profiles reveal sex-related oxidative stress imbalance in de novo drug-naive Parkinson's disease patients

Author

European Commission, Meoni, Gaia [0000-0002-8608-4641], Tenori, Leonardo [0000-0001-6438-059X], Schade, Sebastian [0000-0002-6316-6804], Turano, Paola [0000-0002-7683-8614], Meoni, Gaia, Tenori, Leonardo, Schade, Sebastian, Licari, Cristina, Pirazzini, Chiara, Bacalini, Maria Giulia, Garagnani, Paolo, Turano, Paola, Trenkwalder, Claudia, PROPAG-AGEING Consortium, Franceschi, Claudio, Mollenhauer, Brit, Luchinat, Claudio, European Commission, Meoni, Gaia [0000-0002-8608-4641], Tenori, Leonardo [0000-0001-6438-059X], Schade, Sebastian [0000-0002-6316-6804], Turano, Paola [0000-0002-7683-8614], Meoni, Gaia, Tenori, Leonardo, Schade, Sebastian, Licari, Cristina, Pirazzini, Chiara, Bacalini, Maria Giulia, Garagnani, Paolo, Turano, Paola, Trenkwalder, Claudia, PROPAG-AGEING Consortium, Franceschi, Claudio, Mollenhauer, Brit, and Luchinat, Claudio

Abstract

Parkinson's disease (PD) is the neurological disorder showing the greatest rise in prevalence from 1990 to 2016. Despite clinical definition criteria and a tremendous effort to develop objective biomarkers, precise diagnosis of PD is still unavailable at early stage. In recent years, an increasing number of studies have used omic methods to unveil the molecular basis of PD, providing a detailed characterization of potentially pathological alterations in various biological specimens. Metabolomics could provide useful insights to deepen our knowledge of PD aetiopathogenesis, to identify signatures that distinguish groups of patients and uncover responsive biomarkers of PD that may be significant in early detection and in tracking the disease progression and drug treatment efficacy. The present work is the first large metabolomic study based on nuclear magnetic resonance (NMR) with an independent validation cohort aiming at the serum characterization of de novo drug-naive PD patients. Here, NMR is applied to sera from large training and independent validation cohorts of German subjects. Multivariate and univariate approaches are used to infer metabolic differences that characterize the metabolite and the lipoprotein profiles of newly diagnosed de novo drug-naive PD patients also in relation to the biological sex of the subjects in the study, evidencing a more pronounced fingerprint of the pathology in male patients. The presence of a validation cohort allowed us to confirm altered levels of acetone and cholesterol in male PD patients. By comparing the metabolites and lipoproteins levels among de novo drug-naive PD patients, age- and sex-matched healthy controls, and a group of advanced PD patients, we detected several descriptors of stronger oxidative stress.

Published
2022

2. Metabolite and lipoprotein profiles reveal sex-related oxidative stress imbalance in de novo drug-naive Parkinson's disease patients

Author

Meoni, Gaia, Tenori, Leonardo, Schade, Sebastian, Licari, Cristina, Pirazzini, Chiara, Bacalini, Maria Giulia, Garagnani, Paolo, Turano, Paola, Baldelli, Luca, Jesús, Silvia, Schreglmann, Sebastian R, Sambati, Luisa, Gómez-Garre, Pilar, Halsband, Claire, Calandra-Buonaura, Giovanna, Adarmes-Gómez, Astrid Daniela, Sixel-Döring, Friederike, Zenesini, Corrado, Bhatia, Kailash P., Cortelli, Pietro, Mollenhauer, Brit, Franceschi, Claudio, Houlden, Henry, Liò, Pietro, Luchinat, Claudio, Delledonne, Massimo, Mills, Kevin, Pedersen, Nancy L., Azevedo, Tiago, Bartoletti-Stella, Anna, Bonilla-Toribio, Marta, Buiza-Rueda, Dolores, Capellari, Sabina, Carriòn-Claro, Mario, Clayton, Robert, Dal Molin, Alessandra, Dimitri, Giovanna Maria, Doykov, Ivan, Giuliani, Cristina, Hägg, Sara, Hällqvist, Jenny, Heywood, Wendy, Huertas, Ismael, Jylhävä, Juulia, Labrador-Espinosa, Miguel A., Macias, Daniel, Magrinelli, Francesca, Rodríguez, Juan Francisco Martín, Maturo, Maria Giovanna, Mengozzi, Giacomo, Milazzo, Maddalena, Nardini, Christine, Periñán-Tocino, Maria Teresa, Ravaioli, Francesco, Sala, Claudia, Spasov, Simeon, Tejera-Parrado, Cristina, Paola, Turano, Williams, Dylan, Xumerle, Luciano, Trenkwalder, Claudia, European Commission, Meoni, Gaia, Tenori, Leonardo, Schade, Sebastian, Turano, Paola, Licari, Cristina, Pirazzini, Chiara, Bacalini, Maria Giulia, Garagnani, Paolo, PROPAG-AGEING Consortium[.., Giuliani, Cristina, Provini, Federica, Calandra Buonaura, Giovanna, Cortelli, Pietro, Capellari, Sabina, ], Trenkwalder, Claudia, Franceschi, Claudio, Mollenhauer, Brit, Luchinat, Claudio, [Meoni, Gaia] Univ Florence, Magnet Resonance Ctr CERM, Florence, Italy, [Tenori, Leonardo] Univ Florence, Magnet Resonance Ctr CERM, Florence, Italy, [Licari, Cristina] Univ Florence, Magnet Resonance Ctr CERM, Florence, Italy, [Turano, Paola] Univ Florence, Magnet Resonance Ctr CERM, Florence, Italy, [Luchinat, Claudio] Univ Florence, Magnet Resonance Ctr CERM, Florence, Italy, [Meoni, Gaia] Univ Florence, Dept Chem Ugo Schiff, Florence, Italy, [Tenori, Leonardo] Univ Florence, Dept Chem Ugo Schiff, Florence, Italy, [Licari, Cristina] Univ Florence, Dept Chem Ugo Schiff, Florence, Italy, [Turano, Paola] Univ Florence, Dept Chem Ugo Schiff, Florence, Italy, [Luchinat, Claudio] Univ Florence, Dept Chem Ugo Schiff, Florence, Italy, [Tenori, Leonardo] Consorzio Interuniv Risonanze Magnet Met Prot CIR, Florence, Italy, [Turano, Paola] Consorzio Interuniv Risonanze Magnet Met Prot CIR, Florence, Italy, [Luchinat, Claudio] Consorzio Interuniv Risonanze Magnet Met Prot CIR, Florence, Italy, [Schade, Sebastian] Univ Med Ctr Goettingen, Dept Clin Neurophysiol, Gottingen, Germany, [Pirazzini, Chiara] IRCCS Ist Sci Neurol Bologna, Bologna, Italy, [Bacalini, Maria Giulia] IRCCS Ist Sci Neurol Bologna, Bologna, Italy, [Garagnani, Paolo] Univ Bologna, Dept Expt Diagnost & Specialty Med DIMES, Bologna, Italy, [Franceschi, Claudio] Univ Bologna, Dept Expt Diagnost & Specialty Med DIMES, Bologna, Italy, [Trenkwalder, Claudia] Univ Med Ctr Goettingen, Dept Neurol & Paracelsus Elena Klin, Kassel, Germany, [Mollenhauer, Brit] Univ Med Ctr Goettingen, Dept Neurol & Paracelsus Elena Klin, Kassel, Germany, [Franceschi, Claudio] Lobachevsky Univ, Lab Syst Med Hlth Aging, Nizhnii Novgorod, Russia, [Franceschi, Claudio] Lobachevsky Univ, Dept Appl Math, Nizhnii Novgorod, Russia, Instruct-ERIC, a Landmark ESFRI project, CERM/CIRMMP Italy Centre, Horizon 2020 Framework Programme (PROPAG-AGEING), Meoni, Gaia [0000-0002-8608-4641], Tenori, Leonardo [0000-0001-6438-059X], Schade, Sebastian [0000-0002-6316-6804], Turano, Paola [0000-0002-7683-8614], Franceschi, Claudio [0000-0001-9841-6386], Luchinat, Claudio [0000-0003-2271-8921], and Apollo - University of Cambridge Repository

Subjects
Risk, Metabolites, ipoproteins, sex-related, oxidative stress imbalance, Parkinson’s disease, NMR, Parkinson's disease, Serum-cholesterol, Predictive markers, Levodopa, Cellular and Molecular Neuroscience, Plasma, RC346-429, Homocysteine, Cholesterol levels, PROPAG-AGEING Consortium, Diagnostic markers, metabolomics, Nmr, Phenotypes, Neurology, PD, Neurology. Diseases of the nervous system, Neurology (clinical), Biomarkers
Abstract

Parkinson's disease (PD) is the neurological disorder showing the greatest rise in prevalence from 1990 to 2016. Despite clinical definition criteria and a tremendous effort to develop objective biomarkers, precise diagnosis of PD is still unavailable at early stage. In recent years, an increasing number of studies have used omic methods to unveil the molecular basis of PD, providing a detailed characterization of potentially pathological alterations in various biological specimens. Metabolomics could provide useful insights to deepen our knowledge of PD aetiopathogenesis, to identify signatures that distinguish groups of patients and uncover responsive biomarkers of PD that may be significant in early detection and in tracking the disease progression and drug treatment efficacy. The present work is the first large metabolomic study based on nuclear magnetic resonance (NMR) with an independent validation cohort aiming at the serum characterization of de novo drug-naive PD patients. Here, NMR is applied to sera from large training and independent validation cohorts of German subjects. Multivariate and univariate approaches are used to infer metabolic differences that characterize the metabolite and the lipoprotein profiles of newly diagnosed de novo drug-naive PD patients also in relation to the biological sex of the subjects in the study, evidencing a more pronounced fingerprint of the pathology in male patients. The presence of a validation cohort allowed us to confirm altered levels of acetone and cholesterol in male PD patients. By comparing the metabolites and lipoproteins levels among de novo drug-naive PD patients, age- and sex-matched healthy controls, and a group of advanced PD patients, we detected several descriptors of stronger oxidative stress., This work was supported by the Horizon 2020 Framework Programme (grant number 634821, PROPAG-AGEING).

Published
2022

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