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1. Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson's disease patients.

Author

Zago E, Dal Molin A, Dimitri GM, Xumerle L, Pirazzini C, Bacalini MG, Maturo MG, Azevedo T, Spasov S, Gómez-Garre P, Periñán MT, Jesús S, Baldelli L, Sambati L, Calandra-Buonaura G, Garagnani P, Provini F, Cortelli P, Mir P, Trenkwalder C, Mollenhauer B, Franceschi C, Liò P, and Nardini C

Subjects
Aged, Biomarkers blood, Cohort Studies, Female, Humans, Male, Middle Aged, Aging metabolism, MicroRNAs blood, Parkinson Disease metabolism
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., (© 2022. The Author(s).)

Published
2022
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2. A geroscience approach for Parkinson's disease: Conceptual framework and design of PROPAG-AGEING project.

Author

Pirazzini C, Azevedo T, Baldelli L, Bartoletti-Stella A, Calandra-Buonaura G, Dal Molin A, Dimitri GM, Doykov I, Gómez-Garre P, Hägg S, Hällqvist J, Halsband C, Heywood W, Jesús S, Jylhävä J, Kwiatkowska KM, Labrador-Espinosa MA, Licari C, Maturo MG, Mengozzi G, Meoni G, Milazzo M, Periñán-Tocino MT, Ravaioli F, Sala C, Sambati L, Schade S, Schreglmann S, Spasov S, Tenori L, Williams D, Xumerle L, Zago E, Bhatia KP, Capellari S, Cortelli P, Garagnani P, Houlden H, Liò P, Luchinat C, Delledonne M, Mills K, Mir P, Mollenhauer B, Nardini C, Pedersen NL, Provini F, Strom S, Trenkwalder C, Turano P, Bacalini MG, and Franceschi C

Subjects
Aged, Aged, 80 and over, Female, Humans, Male, Age Factors, Case-Control Studies, Europe, Genomics, Metabolomics, Motor Activity, Nerve Degeneration, Research Design, Signal Transduction, Twin Studies as Topic, Aging genetics, Aging metabolism, Aging pathology, Biomedical Research, Brain metabolism, Brain pathology, Brain physiopathology, Geriatrics, Inflammation Mediators metabolism, Neurons metabolism, Neurons pathology, Parkinson Disease genetics, Parkinson Disease metabolism, Parkinson Disease pathology, Parkinson Disease physiopathology
Abstract

Advanced age is the major risk factor for idiopathic Parkinson's disease (PD), but to date the biological relationship between PD and ageing remains elusive. Here we describe the rationale and the design of the H2020 funded project "PROPAG-AGEING", whose aim is to characterize the contribution of the ageing process to PD development. We summarize current evidences that support the existence of a continuum between ageing and PD and justify the use of a Geroscience approach to study PD. We focus in particular on the role of inflammaging, the chronic, low-grade inflammation characteristic of elderly physiology, which can propagate and transmit both locally and systemically. We then describe PROPAG-AGEING design, which is based on the multi-omic characterization of peripheral samples from clinically characterized drug-naïve and advanced PD, PD discordant twins, healthy controls and "super-controls", i.e. centenarians, who never showed clinical signs of motor disability, and their offspring. Omic results are then validated in a large number of samples, including in vitro models of dopaminergic neurons and healthy siblings of PD patients, who are at higher risk of developing PD, with the final aim of identifying the molecular perturbations that can deviate the trajectories of healthy ageing towards PD development., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2021
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3. Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson's disease patients

Author

Zago E., Dal Molin A., Dimitri G. M., Xumerle L., Pirazzini C., Bacalini M. G., Maturo M. G., Azevedo T., Spasov S., Gomez-Garre P., Perinan M. T., Jesus S., Baldelli L., Sambati L., Calandra Buonaura G., Garagnani P., Provini F., Cortelli P., Mir P., Trenkwalder C., Mollenhauer B., Franceschi C., Lio P., Nardini C., Adarmes-Gomez A., Bartoletti-Stella A., Bhatia K. P., Marta B. -T., Boninsegna C., Broli M., Dolores B. -R., Calandra-Buonaura G., Capellari S., Carrion-Claro M., Cilea R., Clayton R., Molin A. D., De Luca S., De Massis P., Doykov I., Escuela-Martin R., Fabbri G., Gabellini A., Giuliani C., Guaraldi P., Hagg S., Hallqvist J., Halsband C., Heywood W., Houlden H., Huertas I., Jylhava J., Labrador-Espinosa M. A., Licari C., Luchinat C., Macias D., Macri S., Magrinelli F., Rodriguez J. F. M., Massimo D., Mengozzi G., Meoni G., Mignani F., Milazzo M., Mills K., Nassetti S. A., Pedersen N. L., Perinan-Tocino M. T., Ravaioli F., Sala C., Scaglione C. L. M., Schade S., Schreglmann S., Strom S., Tejera-Parrado C., Tenori L., Turano P., Valzania F., Ortega R. V., Williams D., Apollo - University of Cambridge Repository, Zago E., Dal Molin A., Dimitri G.M., Xumerle L., Pirazzini C., Bacalini M.G., Maturo M.G., Azevedo T., Spasov S., Gomez-Garre P., Perinan M.T., Jesus S., Baldelli L., Sambati L., Calandra Buonaura G., Garagnani P., Provini F., Cortelli P., Mir P., Trenkwalder C., Mollenhauer B., Franceschi C., Lio P., Nardini C., Adarmes-Gomez A., Bartoletti-Stella A., Bhatia K.P., Marta B.-T., Boninsegna C., Broli M., Dolores B.-R., Calandra-Buonaura G., Capellari S., Carrion-Claro M., Cilea R., Clayton R., Molin A.D., De Luca S., De Massis P., Doykov I., Escuela-Martin R., Fabbri G., Gabellini A., Giuliani C., Guaraldi P., Hagg S., Hallqvist J., Halsband C., Heywood W., Houlden H., Huertas I., Jylhava J., Labrador-Espinosa M.A., Licari C., Luchinat C., Macias D., Macri S., Magrinelli F., Rodriguez J.F.M., Massimo D., Mengozzi G., Meoni G., Mignani F., Milazzo M., Mills K., Nassetti S.A., Pedersen N.L., Perinan-Tocino M.T., Ravaioli F., Sala C., Scaglione C.L.M., Schade S., Schreglmann S., Strom S., Tejera-Parrado C., Tenori L., Turano P., Valzania F., Ortega R.V., and Williams D.

Subjects
Male, Aging, Molecular biology, Science, Immunology, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Medical research, Humans, Parkinson, 030304 developmental biology, Aged, 0303 health sciences, Multidisciplinary, Biological techniques, Parkinson Disease, Middle Aged, 3. Good health, nervous system diseases, Computational biology and bioinformatics, MicroRNAs, Neurology, ageing, Medicine, Female, 030217 neurology & neurosurgery, Biomarkers
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., This work was supported by the Horizon 2020 Framework Programme (Grant number 634821, PROPAG-AGING).

Published
2022

4. Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients

Author

Baldelli, Luca, Schade, Sebastian, Jesús, Silvia, Schreglmann, Sebastian R., Sambati, Luisa, Gómez-Garre, Pilar, Halsband, Claire, Calandra-Buonaura, Giovanna, Adarmes-Gómez, Astrid Daniela, Sixel-Döring, Friederike, Zenesini, Corrado, Pirazzini, Chiara, Garagnani, Paolo, Bacalini, Maria Giulia, 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., Licari, Cristina, Macias, Daniel, Magrinelli, Francesca, Rodríguez, Juan Francisco Martín, Maturo, Maria Giovanna, Mengozzi, Giacomo, Meoni, Gaia, Milazzo, Maddalena, Nardini, Christine, Periñán-Tocino, Maria Teresa, Ravaioli, Francesco, Sala, Claudia, Spasov, Simeon, Tejera-Parrado, Cristina, Tenori, Leonardo, Paola, Turano, Williams, Dylan, Xumerle, Luciano, Zago, Elisa, Broli, Marcella, De Massis, Patrizia, Escuela-Martin, Rocio, Fabbri, Giovanni, Gabellini, Anna, Guaraldi, Pietro, Macrì, Stefania, Nassetti, Stefania Alessandra, Scaglione, Cesa Lorella Maria, Valzania, Franco, Rosaria, Cilea, Mignani, Francesco, Ortega, Rosario Vigo, Boninsegna, Claudia, De Luca, Silvia, Mir, Pablo, Trenkwalder, Claudia, Provini, Federica, European Commission, Schade, Sebastian [0000-0002-6316-6804], Gómez-Garre, Pilar [0000-0002-0437-6182], Mir, Pablo [0000-0003-1656-302X], Provini, Federica [0000-0001-9063-2658], Apollo - University of Cambridge Repository, Baldelli L., Schade S., Jesus S., Schreglmann S.R., Sambati L., Gomez-Garre P., Halsband C., Calandra Buonaura G., Adarmes-Gomez A.D., Sixel-Doring F., Zenesini C., Pirazzini C., Garagnani P., Bacalini M.G., Bhatia K.P., Cortelli P., Mollenhauer B., Franceschi C., Houlden H., Lio P., Luchinat C., Delledonne M., Mills K., Pedersen N.L., Azevedo T., Bartoletti-Stella A., Bonilla-Toribio M., Buiza-Rueda D., Capellari S., Carrion-Claro M., Clayton R., Dal Molin A., Dimitri G.M., Doykov I., Giuliani C., Hagg S., Hallqvist J., Heywood W., Huertas I., Jylhava J., Labrador-Espinosa M.A., Licari C., Macias D., Magrinelli F., Rodriguez J.F.M., Maturo M.G., Mengozzi G., Meoni G., Milazzo M., Nardini C., Perinan-Tocino M.T., Ravaioli F., Sala C., Spasov S., Tejera-Parrado C., Tenori L., Paola T., Williams D., Xumerle L., Zago E., Broli M., De Massis P., Escuela-Martin R., Fabbri G., Gabellini A., Guaraldi P., Macri S., Nassetti S.A., Scaglione C.L.M., Valzania F., Rosaria C., Mignani F., Ortega R.V., Boninsegna C., De Luca S., Mir P., Trenkwalder C., and Provini F.

Subjects
Pediatrics, medicine.medical_specialty, Parkinson's disease, MathematicsofComputing_GENERAL, Disease, prodromal symptom, Predictive markers, REM sleep behavior disorder, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Orthostatic vital signs, 0302 clinical medicine, 030225 pediatrics, Medicine, Motor Manifestations, Disease markers, RC346-429, siblings, business.industry, TheoryofComputation_GENERAL, Cognition, Parkinson Disease, medicine.disease, 3. Good health, metabolomics, parkinson disease, Neurology, Risk factors, Cohort, PD, Neurology. Diseases of the nervous system, Neurology (clinical), PROPAG-AGEING consortium, business, 030217 neurology & neurosurgery
Abstract

PROPAG-AGEING consortium., A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had, This project has received funding from the European Union’s Horizon 2020 research and innovation program Propag‐Ageing under grant agreement no. 634821.

Published
2021
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5. A geroscience approach for Parkinson's disease: Conceptual framework and design of PROPAG-AGEING project

Author

Chiara Pirazzini, Tiago Azevedo, Luca Baldelli, Anna Bartoletti-Stella, Giovanna Calandra-Buonaura, Alessandra Dal Molin, Giovanna Maria Dimitri, Ivan Doykov, Pilar Gómez-Garre, Sara Hägg, Jenny Hällqvist, Claire Halsband, Wendy Heywood, Silvia Jesús, Juulia Jylhävä, Katarzyna Malgorzata Kwiatkowska, Miguel A. Labrador-Espinosa, Cristina Licari, Maria Giovanna Maturo, Giacomo Mengozzi, Gaia Meoni, Maddalena Milazzo, Maria Teresa Periñán-Tocino, Francesco Ravaioli, Claudia Sala, Luisa Sambati, Sebastian Schade, Sebastian Schreglmann, Simeon Spasov, Leonardo Tenori, Dylan Williams, Luciano Xumerle, Elisa Zago, Kailash P. Bhatia, Sabina Capellari, Pietro Cortelli, Paolo Garagnani, Henry Houlden, Pietro Liò, Claudio Luchinat, Massimo Delledonne, Kevin Mills, Pablo Mir, Brit Mollenhauer, Christine Nardini, Nancy L. Pedersen, Federica Provini, Stephen Strom, Claudia Trenkwalder, Paola Turano, Maria Giulia Bacalini, Claudio Franceschi, Astrid Adarmes-Gómez, Marta Bonilla-Toribio, Claudia Boninsegna, Marcella Broli, Dolores Buiza-Rueda, Mario Carrión-Claro, Rosalia Cilea, Robert Clayton, Silvia De Luca, Patrizia De Massis, Rocio Escuela-Martin, Giovanni Fabbri, Anna Gabellini, Cristina Giuliani, Pietro Guaraldi, Ismae Huertas, Daniel Macias, Stefania Macrì, Francesca Magrinelli, Juan Francisco Martín Rodríguez, Francesco Mignani, Stefania Alessandra Nassetti, Cesa Lorella Maria Scaglione, Cristina Tejera-Parrado, Franco Valzania, Rosario Vigo Ortega, Pirazzini C., Azevedo T., Baldelli L., Bartoletti-Stella A., Calandra Buonaura G., Dal Molin A., Dimitri G.M., Doykov I., Gomez-Garre P., Hagg S., Hallqvist J., Halsband C., Heywood W., Jesus S., Jylhava J., Kwiatkowska K.M., Labrador-Espinosa M.A., Licari C., Maturo M.G., Mengozzi G., Meoni G., Milazzo M., Perinan-Tocino M.T., Ravaioli F., Sala C., Sambati L., Schade S., Schreglmann S., Spasov S., Tenori L., Williams D., Xumerle L., Zago E., Bhatia K.P., Capellari S., Cortelli P., Garagnani P., Houlden H., Lio P., Luchinat C., Delledonne M., Mills K., Mir P., Mollenhauer B., Nardini C., Pedersen N.L., Provini F., Strom S., Trenkwalder C., Turano P., Bacalini M.G., Franceschi C., Adarmes-Gomez A., Bonilla-Toribio M., Boninsegna C., Broli M., Buiza-Rueda D., Carrion-Claro M., Cilea R., Clayton R., Molin A.D., De Luca S., De Massis P., Escuela-Martin R., Fabbri G., Gabellini A., Giuliani C., Guaraldi P., Huertas I., Macias D., Macri S., Magrinelli F., Rodriguez J.F.M., Mignani F., Nassetti S.A., Scaglione C.L.M., Tejera-Parrado C., Valzania F., and Ortega R.V.

Subjects
0301 basic medicine, Gerontology, Male, Aging, Parkinson's disease, Biomedical Research, Inflammaging, Neurodegeneration, Omics, Disease, Motor Activity, 03 medical and health sciences, 0302 clinical medicine, Omic, medicine, Humans, Metabolomics, Risk factor, Aged, Aged, 80 and over, Neurons, Geroscience, business.industry, Age Factors, Brain, Parkinson Disease, Genomics, medicine.disease, 3. Good health, Europe, 030104 developmental biology, Conceptual framework, Ageing, Geriatrics, Research Design, Case-Control Studies, Nerve Degeneration, Twin Studies as Topic, Female, Healthy ageing, Inflammation Mediators, business, 030217 neurology & neurosurgery, Motor disability, Developmental Biology, Signal Transduction
Abstract

Advanced age is the major risk factor for idiopathic Parkinson's disease (PD), but to date the biological relationship between PD and ageing remains elusive. Here we describe the rationale and the design of the H2020 funded project "PROPAG-AGEING", whose aim is to characterize the contribution of the ageing process to PD development. We summarize current evidences that support the existence of a continuum between ageing and PD and justify the use of a Geroscience approach to study PD. We focus in particular on the role of inflammaging, the chronic, low-grade inflammation characteristic of elderly physiology, which can propagate and transmit both locally and systemically. We then describe PROPAG-AGEING design, which is based on the multi-omic characterization of peripheral samples from clinically characterized drug-naive and advanced PD, PD discordant twins, healthy controls and "super-controls", i.e. centenarians, who never showed clinical signs of motor disability, and their offspring. Omic results are then validated in a large number of samples, including in vitro models of dopaminergic neurons and healthy siblings of PD patients, who are at higher risk of developing PD, with the final aim of identifying the molecular perturbations that can deviate the trajectories of healthy ageing towards PD development.

Published
2020
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