A geroscience approach for Parkinson’s disease: Conceptual framework and design of PROPAG-AGEING project

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

doi:10.1016/j.mad.2020.111426

Cited by 14 publications

(16 citation statements)

References 83 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 . The subjects in this study are a subset of the cohorts analyzed in the H2020 Project “PROPAG-AGEING” ( www.propag-ageing.eu/project ) 27 . To our best knowledge, this is the first large NMR-based study with an independent validation cohort aiming at the serum characterization of dn 2 PD patients.…”

Section: Introductionmentioning

confidence: 99%

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

Tenori

Schade

Licari

et al. 2022

npj Parkinsons Dis.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Tenori

Schade

Licari

et al. 2022

npj Parkinsons Dis.

Self Cite

View full text Add to dashboard Cite

show abstract

“…As a consequence, ageing represents a crucial variable to understand PD pathogenesis, to identify early biomarkers of the disease and to promote innovative therapies 2 . This is the perspective and the central rationale behind the project PROPAG-AGEING (“ The continuum between healthy ageing and idiopathic Parkinson Disease within a propagation perspective of inflammation and damage: the search for new diagnostic, prognostic and therapeutic targets ”), set up to elucidate the contribution of ageing to PD 3 . PROPAG-AGEING envisages a multi-omic characterization of peripheral biospecimens of PD patients (both de novo, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…As previously reported 4 , 5 , the strategy to consider a continuum of phenotypes (advanced stage patients, early stage patients, controls and super-controls) enhances the possibility to identify biomarkers and to understand the pathogenesis of diseases. Furthermore, PROPAG-AGEING has recruited a cohort of siblings of PD patients that includes unaffected subjects having a higher risk for developing PD compared to the general population 3 .…”

Section: Introductionmentioning

confidence: 99%

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

Periñán

Adarmes‐Gómez²,

Azevedo

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…The inclusion bodies in DAergic neurons, referred to as Lewy bodies, and their main protein component, α-synuclein (α-Syn), are the prominent neuropathological features of this disease [6]. The recently established PROPAG-AGEING project aims to characterize the contribution of the aging process to the development of PD [7]. A previous study showed that aged rats exhibited a higher susceptibility to neurotoxin 6-hydroxydopamine (6-OHDA) to produce a PD model than young rats [8].…”

Section: Introductionmentioning

confidence: 99%

Dual Roles of Microglia in the Basal Ganglia in Parkinson’s Disease

Choudhury

Kigami

Tanaka

2021

IJMS

View full text Add to dashboard Cite

With the increasing age of the population, the incidence of Parkinson’s disease (PD) has increased exponentially. The development of novel therapeutic interventions requires an understanding of the involvement of senescent brain cells in the pathogenesis of PD. In this review, we highlight the roles played by microglia in the basal ganglia in the pathophysiological processes of PD. In PD, dopaminergic (DAergic) neuronal degeneration in the substantia nigra pars compacta (SNc) activates the microglia, which then promote DAergic neuronal degeneration by releasing potentially neurotoxic factors, including nitric oxide, cytokines, and reactive oxygen species. On the other hand, microglia are also activated in the basal ganglia outputs (the substantia nigra pars reticulata and the globus pallidus) in response to excess glutamate released from hyperactive subthalamic nuclei-derived synapses. The activated microglia then eliminate the hyperactive glutamatergic synapses. Synapse elimination may be the mechanism underlying the compensation that masks the appearance of PD symptoms despite substantial DAergic neuronal loss. Microglial senescence may correlate with their enhanced neurotoxicity in the SNc and the reduced compensatory actions in the basal ganglia outputs. The dual roles of microglia in different basal ganglia regions make it difficult to develop interventions targeting microglia for PD treatment.

show abstract

A geroscience approach for Parkinson’s disease: Conceptual framework and design of PROPAG-AGEING project

Cited by 14 publications

References 83 publications

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

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

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

Dual Roles of Microglia in the Basal Ganglia in Parkinson’s Disease

Contact Info

Product

Resources

About