Higher senescence associated secretory phenotype and lower defense mediator in urinary extracellular vesicles of elders with and without Parkinson disease

Yeh, Shu-Hui; Lin, Chia-Hsueh; Yang, Yun-Jung; Lin, Li‐Wei; Tseng, Chung Jen; Yang, Kuender D.

doi:10.1038/s41598-021-95062-y

Cited by 16 publications

(10 citation statements)

References 43 publications

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“…One study used both CNS‐originating EVs and general EVs for ROC analysis, and we did not exclude it (Yan et al., 2022). Among the studies using general EVs, thirty of those studies did not include an ROC analysis (Athauda et al., 2019; Bhattacharyya et al., 2022; Cerri et al., 2018; Chan et al., 2023; Chan et al., 2021; Chan et al., 2023; Chung et al., 2020; Elkouris et al., 2019; Fraser et al., 2016; Han et al., 2019; Herman et al., 2023; Ho et al., 2014; Hong et al., 2023; Kitamura et al., 2018; Lamontagne‐Proulx et al., 2019; Leng et al., 2020; Leng et al., 2022; Miyamoto et al., 2023; Sproviero et al., 2021; Sproviero et al., 2022; Taymans et al., 2023; Wang et al., 2017; Wang et al., 2018; Wang et al., 2020; Wang et al., 2022; Xia et al., 2019; Yang et al., 2015; Yang et al., 2018; Yeh et al., 2021; Zhao et al., 2020), six did not include sensitivity or specificity (Grossi et al., 2021; Gualerzi et al., 2019; He et al., 2021; Ohmichi et al., 2019; Ruf et al., 2021; Yao et al., 2018), and one study only performed the ROC analysis directly in serum instead of EVs (Citterio et al., 2023). In total, the meta‐analysis included 21 studies (Barbagallo et al., 2020; Cao et al., 2019; Cao et al., 2020; Cao et al., 2017; Chung et al., 2021a; Chung et al., 2021b; Dos Santos et al., 2018; Gui et al., 2015; Hadisurya et al., 2023; Hong et al., 2021; Lucien et al., 2022; Manna et al., 2021; Shim et al., 2021; Stuendl et al., 2016; Stuendl et al.,…”

Section: Resultsmentioning

confidence: 99%

Extracellular vesicles from bodily fluids for the accurate diagnosis of Parkinson's disease and related disorders: A systematic review and diagnostic meta‐analysis

Taha,

Bogoniewski

2023

J of Extracellular Bio

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Parkinsonian disorders, including Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP) are often misdiagnosed due to overlapping symptoms and the absence of precise biomarkers. Furthermore, there are no current methods to ascertain the progression and conversion of prodromal conditions such as REM behaviour disorder (RBD). Extracellular vesicles (EVs), containing a mixture of biomolecules, have emerged as potential sources for parkinsonian diagnostics. However, inconsistencies in previous studies have left their diagnostic potential unclear. We conducted a meta‐analysis, following PRISMA guidelines, to assess the diagnostic accuracy of general EVs isolated from various bodily fluids, including cerebrospinal fluid (CSF), plasma, serum, urine or saliva, in differentiating patients with parkinsonian disorders from healthy controls (HCs). The meta‐analysis included 21 studies encompassing 1285 patients with PD, 24 with MSA, 105 with DLB, 99 with PSP, 101 with RBD and 783 HCs. Further analyses were conducted only for patients with PD versus HCs, given the limited number for other comparisons. Using bivariate and hierarchal receiver operating characteristics (HSROC) models, the meta‐analysis revealed moderate diagnostic accuracy in distinguishing patients with PD from HCs, with substantial heterogeneity and publication bias. The trim‐and‐fill method revealed at least two missing studies with null or low diagnostic accuracy. CSF‐EVs showed better overall diagnostic accuracy, while plasma‐EVs had the lowest performance. General EVs demonstrated higher diagnostic accuracy compared to CNS‐originating EVs, which are more time‐consuming, labour‐ and cost‐intensive to isolate. In conclusion, while holding promise, utilizing biomarkers in general EVs for PD diagnosis remains unfeasible due to existing challenges. The focus should shift toward harmonizing the field through standardization, collaboration, and rigorous validation. Current efforts by the International Society For Extracellular Vesicles (ISEV) aim to enhance the accuracy and reproducibility of EV‐related research through rigor and standardization, aiming to bridge the gap between theory and practical clinical application.

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Section: Resultsmentioning

confidence: 99%

Extracellular vesicles from bodily fluids for the accurate diagnosis of Parkinson's disease and related disorders: A systematic review and diagnostic meta‐analysis

Taha,

Bogoniewski

2023

J of Extracellular Bio

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“…A study showed that SASP cytokines and immune defense factors could be identified in urinary EVs but not in urinary solutions. SASPassociated factors (e.g., IL-8, IP-10, GRO, and MCP-1) were detected at significantly higher levels in urinary EVs from old individuals (age >60) than young adults (Yeh et al, 2021).…”

Section: Cellular Alterations and Molecular Changesmentioning

confidence: 90%

Biomarkers of aging

Bao

Cao

Chen

et al. 2023

Sci. China Life Sci.

153

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Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant. Supporting Information The supporting information is available online at 10.1007/s11427-023-2305-0. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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“…CD63 was the surface protein of exosome, and CD63 was equivalent to an internal reference. It may be related to the age of PD patients [ 45 ]. This data indicated that we use the same amount of exosome to detect miR-184.…”

Section: Discussionmentioning

confidence: 99%

MiR-184 Mediated the Expression of ZNF865 in Exosome to Promote Procession in the PD Model

Liu,

Wang,

et al. 2023

Mol Neurobiol

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Exosomes are nanoscale small vesicles (EVs) secreted by cells that carry important bio information, including proteins, miRNAs, and more. Exosome contents are readily present in body fluids, including blood, and urine of humans and animals, and thereby act as markers of diseases. In patients with Parkinson’s disease (PD), exosomes may spread alpha-synuclein and miR-184 between the cells contributing to dopaminergic neuronal loss. In this study, we detected the levels of miR-184 in urine-excreted neuronal exosomes between PD patients and age-matched healthy subjects by qRT-PCR analysis. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were also used to determine the ultracellular structures of exosomes nanoparticles. MPP + and MPTP were used to construct the cell and animal PD model. Behavioral tests were used to detect motor performance. Furthermore, the cytological experiments were measured to examine the relationship between miR-184 and ZNF865. We found that the levels of miR-184 in urine-derived neuronal exosomes from PD patients were higher, compared to aged-matched normal people. The exosomes from PD patients were larger with greater numbers than those from the age-matched healthy subjects. The difference in miR-184 in urinary exosomes between PD patients and normal people may provide a novel perspective for early diagnosis of PD. However, no difference in CD63 level was observed in Exo-control and Exo-PD groups (exosome from control or PD groups). Moreover, ZNF865 was detected as the targeted gene of miR-184. In addition, miR-184 ASO (miR-184 antisense oligodeoxynucleotide, miR-184 ASO) could rescue the damage of neuronal apoptosis and motor performance in PD mice. Our results showed the miR-184 potential to function as a diagnostic marker of PD. Graphical Abstract

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Higher senescence associated secretory phenotype and lower defense mediator in urinary extracellular vesicles of elders with and without Parkinson disease

Cited by 16 publications

References 43 publications

Extracellular vesicles from bodily fluids for the accurate diagnosis of Parkinson's disease and related disorders: A systematic review and diagnostic meta‐analysis

Extracellular vesicles from bodily fluids for the accurate diagnosis of Parkinson's disease and related disorders: A systematic review and diagnostic meta‐analysis

Biomarkers of aging

MiR-184 Mediated the Expression of ZNF865 in Exosome to Promote Procession in the PD Model

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