1. Mitochondrial Signatures in Circulating Extracellular Vesicles of Older Adults with Parkinson’s Disease: Results from the EXosomes in PArkiNson’s Disease (EXPAND) Study
- Author
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Raffaella Beli, Federico Marini, Anna Picca, Alessandra Biancolillo, Francesco Landi, Cecilia Bucci, Flora Guerra, Giovanni Landi, Maria Rita Lo Monaco, Riccardo Calvani, Anna Rita Bentivoglio, Roberto Bernabei, Emanuele Marzetti, Picca, Anna, Guerra, Flora, Calvani, Riccardo, Marini, Federico, Biancolillo, Alessandra, Landi, Giovanni, Beli, Raffaella, Landi, Francesco, Bernabei, Roberto, Bentivoglio, Anna Rita, Monaco, Maria Rita Lo, Bucci, Cecilia, and Marzetti, Emanuele
- Subjects
mitochondrial-lysosomal axi ,SDHB ,Settore M-PSI/02 - PSICOBIOLOGIA E PSICOLOGIA FISIOLOGICA ,Protein subunit ,lcsh:Medicine ,Inflammation ,exosomes ,Article ,mitochondrial-derived vesicle ,03 medical and health sciences ,0302 clinical medicine ,mitochondrial-derived vesicles ,mitochondrial-lysosomal axis ,mitochondrial dynamic ,medicine ,exosome ,Interleukin 9 ,aging ,biomarkers ,mitochondrial dynamics ,mitochondrial quality control ,mitophagy ,Macrophage inflammatory protein ,030304 developmental biology ,0303 health sciences ,business.industry ,Neurodegeneration ,Settore MED/09 - MEDICINA INTERNA ,lcsh:R ,General Medicine ,Extracellular vesicle ,medicine.disease ,Molecular biology ,nervous system diseases ,biomarker ,Tumor necrosis factor alpha ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Systemic inflammation and mitochondrial dysfunction are involved in neurodegeneration in Parkinson’s disease (PD). Extracellular vesicle (EV) trafficking may link inflammation and mitochondrial dysfunction. In the present study, circulating small EVs (sEVs) from 16 older adults with PD and 12 non-PD controls were purified and characterized. A panel of serum inflammatory biomolecules was measured by multiplex immunoassay. Protein levels of three tetraspanins (CD9, CD63, and CD81) and selected mitochondrial markers (adenosine triphosphate 5A (ATP5A), mitochondrial cytochrome C oxidase subunit I (MTCOI), nicotinamide adenine dinucleotide reduced form (NADH):ubiquinone oxidoreductase subunit B8 (NDUFB8), NADH:ubiquinone oxidoreductase subunit S3 (NDUFS3), succinate dehydrogenase complex iron sulfur subunit B (SDHB), and ubiquinol-cytochrome C reductase core protein 2 (UQCRC2)) were quantified in purified sEVs by immunoblotting. Relative to controls, PD participants showed a greater amount of circulating sEVs. Levels of CD9 and CD63 were lower in the sEV fraction of PD participants, whereas those of CD81 were similar between groups. Lower levels of ATP5A, NDUFS3, and SDHB were detected in sEVs from PD participants. No signal was retrieved for UQCRC2, MTCOI, or NDUFB8 in either participant group. To identify a molecular signature in circulating sEVs in relationship to systemic inflammation, a low level-fused (multi-platform) partial least squares discriminant analysis was applied. The model correctly classified 94.2% ± 6.1% PD participants and 66.7% ± 5.4% controls, and identified seven biomolecules as relevant (CD9, NDUFS3, C-reactive protein, fibroblast growth factor 21, interleukin 9, macrophage inflammatory protein 1β, and tumor necrosis factor alpha). In conclusion, a mitochondrial signature was identified in circulating sEVs from older adults with PD, in association with a specific inflammatory profile. In-depth characterization of sEV trafficking may allow identifying new biomarkers for PD and possible targets for personalized interventions.
- Published
- 2020