MicroRNAs from extracellular vesicles as a signature for Parkinson's disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Caldi Gomes L
PROVIDER: S-EPMC8021010 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
Publications
MicroRNAs from extracellular vesicles as a signature for Parkinson's disease.
Caldi Gomes Lucas L Roser Anna-Elisa AE Jain Gaurav G Pena Centeno Tonatiuh T Maass Fabian F Schilde Lukas L May Caroline C Schneider Anja A Bähr Mathias M Marcus Katrin K Fischer André A Lingor Paul P
Clinical and translational medicine 20210401 4
Similar Datasets
Project description:Small extracellular vesicles (sEVs) are generated by all types of cells during physiological or pathological conditions. There is growing interest in tissue-derived small extracellular vesicles (tdsEVs) because they can be isolated from a single tissue source. Knowing the representation profile of microRNA (miRNA) in midbrain tissue-derived sEVs (bdsEVs) and their roles is imperative for understanding the pathological mechanism and improving the diagnosis and treatment of Parkinson's disease (PD). bdsEVs from a rat model of PD and a sham group were separated and purified using ultracentrifugation, size-exclusion chromatography (SEC), and ultrafiltration. Then, miRNA profiling of bdsEVs in both groups was performed using next-generation sequencing (NGS). The expression levels of 180 miRNAs exhibited significant differences between the two groups, including 114 upregulated and 66 downregulated genes in bdsEVs of PD rats compared with the sham group (p < 0.05). Targets of the differentially expressed miRNAs were predicted by miRanda and RNAhybrid, and their involvement in the signaling pathways and cellular function has been analyzed through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO). Furthermore, we explored the expression levels of miR-103-3p, miR-107-3p, miR-219a-2-3p, and miR-379-5p in bdsEVs, sEVs derived from plasma, and plasma of both groups of rats. Interestingly, the expression levels of miR-103-3p, miR-107-3p, miR-219a-2-3p, and miR-379-5p were elevated in bdsEVs and sEVs from plasma; in contrast, their expression levels were decreased in plasma of the rat model of PD. In summary, miRNAs may play a significant role in the onset and development of PD, and miRNAs need to be selected carefully as a research subject for exploring the pathological mechanism and the potential therapeutic targets and diagnostic markers of PD.
| S-EPMC9935574 | biostudies-literature
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:The application of extracellular vesicles (EVs) as vehicles for anti-Parkinson's agents represents a significant advance, yet their clinical translation is hampered by challenges in efficient brain delivery and complex blood-brain barrier (BBB) targeting strategies. In this study, we engineered dopamine onto the surface of adipose-derived stem cell EVs (Dopa-EVs) utilizing a facile, two-step cross-linking approach. This engineering enhanced neuronal uptake of the EVs in primary neurons and neuroblastoma cells, a process shown to be competitively inhibited by dopamine pretreatment and dopamine receptor antibodies. Notably, Dopa-EVs demonstrated increased brain accumulation in mouse Parkinson's disease (PD) models. Therapeutically, Dopa-EVs administration led to the rescue of dopaminergic neuronal loss and amelioration of behavioural deficits in both 6-hydroxydopamine (6-OHDA) and α-Syn PFF-induced PD models. Furthermore, we observed that Dopa-EVs stimulated autophagy evidenced by the upregulation of Beclin-1 and LC3-II. These findings collectively indicate that surface modification of EVs with dopamine presents a potent strategy for targeting dopaminergic neurons in the brain. The remarkable therapeutic potential of Dopa-EVs, demonstrated in PD models, positions them as a highly promising candidate for PD treatment, offering a significant advance over current therapeutic modalities.
| S-EPMC11621972 | biostudies-literature
Project description:Summary Congenital disorders characterized by the quantitative and qualitative reduction in the number of functional nephrons are the primary cause of chronic kidney disease (CKD) in children. We aimed to describe the alteration of urinary extracellular vesicles (uEVs) associated with decreased renal function during childhood. By nanoparticle tracking analysis and quantitative proteomics, we identified differentially expressed proteins in uEVs in bilateral renal hypoplasia, which is characterized by a congenitally reduced number of nephrons. This expression signature of uEVs reflected decreased renal function in CKD patients by congenital anomalies of the kidney and urinary tract or ciliopathy. As a proof-of-concept, we constructed a prototype ELISA system that enabled the isolation of uEVs and quantitation of expression of molecules representing the signature. The system identified decreased renal function even in its early stage. The uEVs signature could pave the way for non-invasive methods that can complement existing testing methods for diagnosing kidney diseases. Graphical abstract Highlights • Urinary extracellular vesicles (uEVs) are altered in chronic kidney disease (CKD)• Characteristic expression signatures associated with childhood CKD are identified• An ELISA utilizing the signature detected decreased renal function• uEVs signature has potential in diagnosing kidney diseases Health sciences; Nephrology; Biomolecules
| S-EPMC9684058 | 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:Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms, caused by the degeneration and loss of dopaminergic neurons in the substantia nigra. Current therapies are limited to symptom management, unable to prevent neuronal loss or halt the progression of the disease. A significant limitation to more effective treatments is the difficulty of crossing the blood-brain barrier (BBB). Extracellular vesicles (EVs) communication plays a crucial role in several physiological processes within the nervous system. Notably, EVs have the unique ability to cross the BBB, making them a highly promising vehicle for delivering therapeutic agents directly to the brain. Given the rising prevalence of PD, the need for therapies that prevent neuronal death and promote cell survival is urgent. This study explores the potential of neural stem cell-derived extracellular vesicles (NSC-EVs) using two in vitro models of PD. Our findings demonstrate that NSC-EVs significantly enhance the survival of dopaminergic neurons by reducing apoptosis and showing strong neuroprotective effects. Notably, the natural extracellular vesicles used in this study are enriched with Catalase, a potent scavenger protein with antioxidant properties. This natural enrichment further strengthens their neuroprotective capacity, enabling them to mitigate oxidative stress and protect vulnerable neurons. The use of such naturally enriched extracellular vesicles represents a promising approach for developing innovative therapies to effectively combat Parkinson's disease.
| S-EPMC11839983 | biostudies-literature
Project description:BackgroundNeural stem cells (NSCs) have the ability to generate a variety of functional neural cell types and have a high potential for neuronal cell regeneration and recovery. Thus, they been recognized as the best source of cell therapy for neurodegenerative diseases, such as Parkinson's disease (PD). Owing to the possibility of paracrine effect-based therapeutic mechanisms and easier clinical accessibility, extracellular vesicles (EVs), which possess very similar bio-functional components from their cellular origin, have emerged as potential alternatives in regenerative medicine.Material and methodsEVs were isolated from human fibroblast (HFF) and human NSC (F3 cells). The supernatant of the cells was concentrated by a tangential flow filtration (TFF) system. Then, the final EVs were isolated using a total EV isolation kit.ResultsIn this study, we demonstrate the potential protective effect of human NSC-derived EVs, showing the prevention of PD pathologies in 6-hydroxydopamine (6-OHDA)-induced in vitro and in vivo mouse models. Human NSC and F3 cell (F3)-derived EVs reduced the intracellular reactive oxygen species (ROS) and associated apoptotic pathways. In addition, F3-derived EVs induced downregulation of pro-inflammatory factors and significantly decreased 6-OHDA-induced dopaminergic neuronal loss in vivo. F3 specific microRNAs (miRNAs) such as hsa-mir-182-5p, hsa-mir-183-5p, hsa-mir-9, and hsa-let-7, which are involved in cell differentiation, neurotrophic function, and immune modulation, were found in F3-derived EVs.ConclusionsWe report that human NSC-derived EVs show an effective neuroprotective property in an in vitro transwell system and in a PD model. The EVs clearly decreased ROS and pro-inflammatory cytokines. Taken together, these results indicate that NSC-derived EVs could potentially help prevent the neuropathology and progression of PD.
| S-EPMC9040239 | biostudies-literature
Project description:BackgroundInflammation contributes substantially to the pathogenesis of Parkinson's disease (PD). Plasma extracellular vesicle (EV)-derived cytokines are emerging biomarkers of inflammation. We conducted a longitudinal study of the plasma EV-derived cytokine profiles of people with PD (PwP).MethodsA total of 101 people with mild to moderate PD and 45 healthy controls (HCs) were recruited, and they completed motor assessments (Unified Parkinson Disease Rating Scale [UPDRS]) and cognitive tests at baseline and 1-year follow-up. We isolated the participants' plasma EVs and analyzed their levels of cytokines, including interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β.ResultsWe noted no significant changes in the plasma EV-derived cytokine profiles of the PwPs and HCs between baseline and the 1-year follow-up. Among the PwP, changes in plasma EV-derived IL-1β, TNF-α and IL-6 levels were significantly associated with changes in the severity of postural instability and gait disturbance (PIGD) and cognition. Baseline plasma EV-derived IL-1β, TNF-α, IL-6, and IL-10 levels were significantly associated with the severity of PIGD and cognitive symptoms at follow-up, and PwP with elevated IL-1β and IL-6 levels exhibited significant progression of PIGD over the study period.ConclusionThese results suggested the role of inflammation in PD progression. In addition, baseline levels of plasma EV-derived proinflammatory cytokines can be used to predict the progression of PIGD, the most severe motor symptom of PD. Additional studies with longer follow-up periods are necessary, and plasma EV-derived cytokines may serve as effective biomarkers of PD progression.
| S-EPMC10042681 | biostudies-literature
Project description:Parkinson's disease (PD) is a neurodegenerative disorder affecting about 10 million people worldwide with a prevalence of about 2% in the over-80 population. The disease brings in also a huge annual economic burden, recently estimated by the Michael J Fox Foundation for Parkinson's Research to be USD 52 billion in the United States alone. Currently, no effective cure exists, but available PD medical treatments are based on symptomatic prescriptions that include drugs, surgical approaches and rehabilitation treatment. Due to the complex biology of a PD brain, the design of clinical trials and the personalization of treatment strategies require the identification of accessible and measurable biomarkers to monitor the events induced by treatment and disease progression and to predict patients' responsiveness. In the present review, we strive to briefly summarize current knowledge about PD biomarkers, focusing on the role of extracellular vesicles as active or involuntary carriers of disease-associated proteins, with particular attention to those research works that envision possible clinical applications.
| S-EPMC10816807 | 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