MicroRNAs from extracellular vesicles as a signature for Parkinson's disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Caldi Gomes L
PROVIDER: S-EPMC8021010 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Extracellular vesicles (EVs) are naturally occurring membranous structures secreted by normal and diseased cells, and carrying a wide range of bioactive molecules. In the central nervous system (CNS), EVs are important in both homeostasis and pathology. Through receptor-ligand interactions, direct fusion, or endocytosis, EVs interact with their target cells. Accumulating evidence indicates that EVs play crucial roles in the pathogenesis of many neurodegenerative disorders (NDs), including Parkinson's disease (PD). PD is the second most common ND, characterized by the progressive loss of dopaminergic (DAergic) neurons within the Substantia Nigra pars compacta (SNpc). In PD, EVs are secreted by both neurons and glial cells, with either beneficial or detrimental effects, via a complex program of cell-to-cell communication. The functions of EVs in PD range from their etiopathogenetic relevance to their use as diagnostic tools and innovative carriers of therapeutics. Because they can cross the blood-brain barrier, EVs can be engineered to deliver bioactive molecules (e.g., small interfering RNAs, catalase) within the CNS. This review summarizes the latest findings regarding the role played by EVs in PD etiology, diagnosis, prognosis, and therapy, with a particular focus on their use as novel PD nanotherapeutics.
| S-EPMC7563168 | biostudies-literature
Project description:BackgroundNeurofilament light chain (NfL) is essential for axonal maintenance and reflects neuronal damage. Extracellular vesicles (EVs), especially exosomes, secreted by cells into the blood, are emerging as novel biomedical research platforms of physiological and pathological processes. The present study investigated the possible association between plasma EV NfL and Parkinson's disease (PD).MethodsOne hundred and sixteen patients with mild to moderate PD and 46 non-PD, neurological controls were recruited, and their clinical motor symptoms and cognitive function were evaluated. Plasma EVs were isolated using an exoEasy kit, and immunomagnetic reduction assay was used to assess EV NfL level. Statistical analysis was performed using SPSS 25.0, and p < 0.05 was considered significant.ResultsThe isolated plasma EVs were validated according to size and the presence of specific surface markers. Compared with the neurological control group, the levels of plasma EV NfL in patients with PD were not significantly different (PD: 9.42 ± 3.89, control: 9.53 ± 3.62 pg/mL plasma, p = 0.71). On the other hand, plasma EV NfL in patients with PD trendwise correlated with the severity of akinetic rigidity (p = 0.05). PD patients with optimal EV NfL (lowest quartile) had 6.66 ± 2.08 lower Unified Parkinson's Disease Rating Scale-III score after adjustment for age, sex, and disease duration.ConclusionPlasma EV NfL levels did not distinguish patients with PD from the neurological control group. The possible correlation between plasma EV NfL with the severity of motor symptoms within the PD patients, especially with akinetic rigidity, was noted. Further clinical validation of the blood EV NfL by a longitudinal follow-up study of PD patients is warranted.
| S-EPMC7724268 | biostudies-literature
Project description:MicroRNAs are small non-protein coding RNAs that regulate gene expression through post-transcriptional repression. Recent studies demonstrated the importance of microRNAs in the nervous system development, function and disease. Parkinson's disease is the second most prevalent neurodegenerative disease with only symptomatic treatment available. Recent success in using small RNAs as therapeutic targets hold a substantial promise for the Parkinson's disease field. Here we review recent work linking the microRNA pathway to Parkinson's disease.
| S-EPMC3163813 | biostudies-literature
Project description: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 1?, 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.
| S-EPMC7074517 | biostudies-literature
Project description:Plasma extracellular vesicles (EVs) containing various molecules, including cytokines, can reflect the intracellular condition and participate in cell-to-cell signaling, thus emerging as biomarkers for Parkinson's disease (PD). Inflammation may be a crucial risk factor for PD development and progression. The present study investigated the role of plasma EV cytokines as the biomarkers of PD. This cross-sectional study recruited 113 patients with PD, with mild to moderate stage disease, and 48 controls. Plasma EVs were isolated, and the levels of cytokines, including pro-interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1, were evaluated. Patients with PD had significantly increased plasma EV pro-IL-1β and TNF-α levels compared with controls after adjustment for age and sex. Despite the lack of a significant association between plasma EV cytokines and motor symptom severity in patients with PD, cognitive dysfunction severity, assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment, was significantly associated with plasma EV pro-IL-1β, IL-6, IL-10, and TNF-α levels. This association was PD specific and not found in controls. Furthermore, patients with PD cognitive deficit (MMSE < 26) exhibited a distinguished EV cytokine profile compared to those without cognitive deficit. The findings support the concept of inflammatory pathogenesis in the development and progression of PD and indicate that plasma EV cytokines may serve as PD biomarkers in future.
| S-EPMC7999703 | biostudies-literature
Project description:Extracellular vesicles (EVs) are submicron-sized lipid envelopes that are produced and released from a parent cell and can be taken up by a recipient cell. EVs are capable of mediating cellular signalling by carrying nucleic acids, proteins, lipids and cellular metabolites between cells and organs. Metabolic dysfunction is associated with changes in plasma concentrations of EVs as well as alterations in their EV cargo. Since EVs can act as messengers between parent and recipient cells, they could be involved in cell-to-cell and organ-to-organ communication in metabolic diseases. Recent literature has shown that EVs are produced by cells within metabolic tissues, such as adipose tissue, pancreas, muscle and liver. These vesicles have therefore been proposed as a novel intercellular communication mode in systemic metabolic regulation. In this review, we will describe and discuss the current literature that investigates the role of adipose-derived EVs in the regulation of obesity-associated metabolic disease. We will particularly focus on the EV-dependent communication between adipocytes, the vasculature and immune cells in type 2 diabetes.
| S-EPMC6861353 | biostudies-literature
Project description:Extracellular vesicles are released by the majority of cell types and circulate in body fluids. They function as a long-distance cell-to-cell communication mechanism that modulates the gene expression profile and fate of target cells. Increasing evidence has established a central role of extracellular vesicles in kidney physiology and pathology. Urinary extracellular vesicles mediate crosstalk between glomerular and tubular cells and between different segments of the tubule, whereas circulating extracellular vesicles mediate organ crosstalk and are involved in the amplification of kidney damage and inflammation. The molecular profile of extracellular vesicles reflects the type and pathophysiological status of the originating cell so could potentially be exploited for diagnostic and prognostic purposes. In addition, robust preclinical data suggest that administration of exogenous extracellular vesicles could promote kidney regeneration and reduce inflammation and fibrosis in acute and chronic kidney diseases. Stem cells are thought to be the most promising source of extracellular vesicles with regenerative activity. Extracellular vesicles are also attractive candidates for drug delivery and various engineering strategies are being investigated to alter their cargo and increase their efficacy. However, rigorous standardization and scalable production strategies will be necessary to enable the clinical application of extracellular vesicles as potential therapeutics.
| S-EPMC9152665 | biostudies-literature
Project description:Extracellular vesicles (EVs) play a central role in intercellular communication, which is relevant for inflammatory and immune processes implicated in neurodegenerative disorders, such as Parkinson's Disease (PD). We characterized and compared distinctive cerebrospinal fluid (CSF)-derived EVs in PD and atypical parkinsonisms (AP), aiming to integrate a diagnostic model based on immune profiling of plasma-derived EVs via artificial intelligence. Plasma- and CSF-derived EVs were isolated from patients with PD, multiple system atrophy (MSA), AP with tauopathies (AP-Tau), and healthy controls. Expression levels of 37 EV surface markers were measured by a flow cytometric bead-based platform and a diagnostic model based on expression of EV surface markers was built by supervised learning algorithms. The PD group showed higher amount of CSF-derived EVs than other groups. Among the 17 EV surface markers differentially expressed in plasma, eight were expressed also in CSF of a subgroup of PD, 10 in MSA, and 6 in AP-Tau. A two-level random forest model was built using EV markers co-expressed in plasma and CSF. The model discriminated PD from non-PD patients with high sensitivity (96.6%) and accuracy (92.6%). EV surface marker characterization bolsters the relevance of inflammation in PD and it underscores the role of EVs as pathways/biomarkers for protein aggregation-related neurodegenerative diseases.
| S-EPMC7996605 | biostudies-literature
Project description:Parkinson's disease (PD) is a disabling neurodegenerative disease that manifests with resting tremor, bradykinesia, rigidity and postural instability. Since the discovery of microRNAs (miRNAs) in 1993, miRNAs have been shown to be important biological molecules involved in diverse processes to maintain normal cellular functions. Over the past decade, many studies have reported dysregulation of miRNA expressions in PD. Here, we identified 15 miRNAs from 34 reported screening studies that demonstrated dysregulation in the brain and/or neuronal models, cerebrospinal fluid (CSF) and blood. Specific miRNAs-of-interest that have been implicated in PD pathogenesis include miR-30, miR-29, let-7, miR-485 and miR-26. However, there are several challenges and limitations in drawing definitive conclusions due to the small sample size in clinical studies, varied laboratory techniques and methodologies and their incomplete penetrance of the blood-brain barrier. Developing an optimal delivery system and unravelling druggable targets of miRNAs in both experimental and human models and clinical validation of the results may pave way for novel therapeutics in PD.
| S-EPMC6888719 | biostudies-literature
Project description:Extracellular vesicles (EVs) are secreted by any neural cells in the central nervous system for molecular clearance, cellular communications, and disease spread in multiple neurodegenerative diseases, including Alzheimer's disease (AD), although their exact molecular mechanism is poorly understood. We hypothesize that high-resolution proteomic profiling of EVs separated from animal models of AD would determine the composition of EV contents and their cellular origin. Here, we examined recently developed transgenic mice (CAST.APP/PS1), which express familial AD-linked mutations of amyloid precursor protein (APP) and presenilin-1 (PS1) in the CAST/EiJ mouse strain and develop hippocampal neurodegeneration. Quantitative proteomics analysis of EVs separated from CAST.APP/PS1 and age-matched control mice by tandem mass tag-mass spectrometry identified a total of 3444 unique proteins, which are enriched in neuron-, astrocyte-, oligodendrocyte-, and microglia-specific molecules. CAST.APP/PS1-derived EVs show significant enrichment of Psen1, APP, and Itgax and reduction of Wdr61, Pmpca, Aldh1a2, Calu, Anp32b, Actn4, and Ndufv2 compared to WT-derived EVs, suggesting the involvement of A?-processing complex and disease-associated/neurodegenerative microglia (DAM/MGnD) in EV secretion. In addition, Itgax and Apoe, DAM/MGnD markers, in EVs show a positive correlation with Itgax and Apoe mRNA expression from brain tissue in CAST.APP/PS1 mice. These datasets indicate the significant contribution of A? plaque and neurodegeneration-induced DAM/MGnD microglia for EV secretion in CAST.APP/PS1 mice and shed light on understanding AD pathogenesis.
| S-EPMC7944570 | biostudies-literature