An miRNA fingerprint using neural-enriched extracellular vesicles from blood plasma: towards a biomarker for amyotrophic lateral sclerosis/motor neuron disease

Open Biology, Год журнала: 2020, Номер 10(6)

Опубликована: Июнь 1, 2020

Biomarkers for amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) are currently not clinically available diagnosis or analysis of progression. If identified, biomarkers could improve patient outcomes by enabling early intervention and assist in the determination treatment efficacy. We hypothesized that neural-enriched extracellular vesicles provide microRNA (miRNA) fingerprints with unequivocal signatures neurodegeneration. Using blood plasma from ALS/MND patients controls, we extracted vesicle fractions conducted next-generation sequencing qPCR miRNA components transcriptome. here report eight sequences which significantly distinguish controls a replicated experiment using second cohort controls. samples may yield unique insights into mechanisms neurodegeneration ALS/MND.

Язык: Английский

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miR-155 as an Important Regulator of Multiple Sclerosis Pathogenesis. A Review

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(9), С. 4332 - 4332

Опубликована: Апрель 21, 2021

Multiple sclerosis (MS) is a chronic, immune-mediated disease and the leading cause of disability among young adults. MicroRNAs (miRNAs) are involved in post-transcriptional regulation gene expression. Of them, miR-155 crucial regulator inflammation plays role modulating autoimmune response MS. blood-brain barrier (BBB) disruption via down-regulation key junctional proteins under inflammatory conditions. It drives demyelination processes by contributing to, e.g., microglial activation, polarization astrocytes, CD47 protein affecting transcription factors. has huge impact on development neuropathic pain indirectly influences regulatory T (Treg) cell differentiation alleviation hypersensitivity. This review also focused neuropsychiatric symptoms appearing as result disease-associated stressors, brain atrophy, pro-inflammatory Recent studies revealed regulating anxiety, stress, hippocampus, treatment-resistant depression. Inhibition expression was demonstrated to be effective preventing pathophysiology aimed support better understanding great dysregulation various aspects MS highlight future perspectives for this molecule.

Язык: Английский

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Small non-coding RNA profiling in patients with non-muscle invasive bladder cancer

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 21, 2025

Язык: Английский

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microRNA and exosome profiling in multiple sclerosis

Multiple Sclerosis Journal, Год журнала: 2020, Номер 26(5), С. 599 - 604

Опубликована: Янв. 22, 2020

New DNA sequencing technologies have uncovered non-coding RNA (ncRNA) as a major player in regulating cellular processes and can no longer be dismissed “junk” or “dark” RNA. Among the ncRNA, microRNA (miRNA) is arguably most extensively characterized category number of studies implicated them critical functions that influence autoimmune demyelination. Of specific interest to multiple sclerosis (MS), miRNA been both immune responses myelination, thus making an attractive candidate for pharmacological intervention disease biomarkers. In addition, exosomes, small vesicles secreted by cell types present all body fluids, also shown play roles signaling, inflammation angiogenesis. Therefore, exosomes are being explored tools therapeutic delivery This article reviews recent advances exosome profiling MS experimental models.

Язык: Английский

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MAGI2-AS3 and miR-374b-5p as Putative Regulators of Multiple Sclerosis via Modulating the PTEN/AKT/IRF-3/IFN-β Axis: New Clinical Insights

ACS Chemical Neuroscience, Год журнала: 2023, Номер 14(6), С. 1107 - 1118

Опубликована: Март 6, 2023

Multiple sclerosis (MS) is a chronic disease and one of the leading causes disability in young adults. The current study aims to investigate pathogenesis MS via studying regulatory role novel lncRNA MAGI2-AS3 miR-374b-5p their downstream targets PTEN/AKT/IRF-3/IFN-β relationship this pathway with severity. Moreover, it assess MAGI2-AS3/miR-374b-5p as diagnostic and/or prognostic biomarkers for MS. Overall, 150 contributors were recruited: 100 patients 50 healthy volunteers. Gene expression MAGI2-AS3, miR-374b-5p, PTEN, AKT, IRF-3 assessed using RT-qPCR, IFN-β was measured by ELISA. Compared control group, serum PTEN downregulated patients, whereas PI3K, IRF-3, upregulated patients. Furthermore, downregulated, while an expanded status scale (EDSS) ≥3.5, compared EDSS <3.5. Receiver-operating-characteristic curve analysis revealed that can be used diagnosis Remarkably, multivariate logistic AKT act independent variables directly correlated inversely EDSS. Regarding positively In conclusion, showed first time crosstalk between could affect AKT/IRF3/IFN-β axis Interestingly, genetic noninvasive

Язык: Английский

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MicroRNAs, Multiple Sclerosis, and Depression

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(15), С. 7802 - 7802

Опубликована: Июль 21, 2021

Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects brain and spinal cord. There are several courses in MS including relapsing–remitting (RRMS), primary progressive (PPMS), secondary (SPMS). Up to 50% patients experience depressive disorders. Major depression (MD) serious comorbidity MS. Many dysfunctions neuroinflammation, peripheral inflammation, gut dysbiosis, oxidative nitrosative stress, neuroendocrine mitochondrial abnormalities may contribute between MD. In addition these actions, medical treatment microRNA (miRNA) regulation also be involved mechanisms study, I review many common miRNA biomarkers for both diseases. These help further explore association

Язык: Английский

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Differential Expression of Serum Extracellular Vesicle miRNAs in Multiple Sclerosis: Disease-Stage Specificity and Relevance to Pathophysiology

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1664 - 1664

Опубликована: Янв. 31, 2022

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Its first clinical presentation (clinically isolated syndrome, CIS) often followed by development relapsing-remitting MS (RRMS). The periphery-to-CNS transmission molecules major pathophysiological pathway in MS. This could include signalling via extracellular vesicle (EV) microRNAs (miRNAs). In this study, we investigated serum EV miRNome CIS and RRMS patients matched controls, with aims to identify stage-specific differentially expressed miRNAs investigate their biomarker potential relevance. miRNA sequencing was conducted on EVs from CIS-remission, RRMS-relapse, viral CNS disorder patients, as well healthy hospitalized controls. Differential expression analysis conducted, predictive power target-pathway analysis. A moderate number dysregulated were identified CIS-remission RRMS-relapse especially relative Some these also between two stages had for patient-control CIS-RRMS separations. For mRNA targets RRMS-relapse-specific miRNAs, biological processes inherent pathophysiology using silico Study findings demonstrate that specific have contribute identification novel, efficacious therapies.

Язык: Английский

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Emerging Biomarkers of Multiple Sclerosis in the Blood and the CSF: A Focus on Neurofilaments and Therapeutic Considerations

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(6), С. 3383 - 3383

Опубликована: Март 21, 2022

Introduction: Multiple Sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of central nervous system (CNS) affecting young people. This due to permanent disability, cognitive impairment, and enormous detrimental impact MS can exert on a patient’s health-related quality life. It great importance recognise it in time commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim reduce activity thus halt disability development, which current clinical practice are monitored by imaging parameters but not biomarkers found blood and/or cerebrospinal fluid (CSF). Both radiological measures routinely monitor lack information fundamental pathophysiological features mechanisms MS. Furthermore, they lag behind process itself. By relapse becomes evident or new lesion appears MRI scan, potentially irreversible damage has already occurred CNS. In recent years, several that previously have been linked other neurological immunological diseases received increased attention Additionally, novel, potential with prognostic diagnostic properties detected CSF patients. Areas covered: this review, we summarise up-to-date knowledge research conducted known promising biomarker candidates Discussion: criteria relies three pillars: imaging, events, presence oligoclonal bands (which was reinstated into revision). Even though McDonald made diagnosis faster than prior iteration, still infallible toolset, especially very stage clinically isolated syndrome. Together gold standard measures, ancillary may just improve accuracy speed well become agents therapeutic efficacy make even more personalised reality near future. major disadvantage these past need obtain measure them. However, advances extremely sensitive immunoassays their measurement possible from peripheral when present only minuscule concentrations. should mark beginning utilisation era

Язык: Английский

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Advances in Gene Therapy for Neurologic Disorders: An Overview

BIO Integration, Год журнала: 2025, Номер 6(1)

Опубликована: Янв. 1, 2025

Neurologic disorders currently affect approximately 100 million people worldwide. most often occur due to inherent genetic mutations, which lead numerous types of functional disruptions in nervous system development. disease-related events, such as and epigenetic changes, cause inflammatory processes the area may enhance disease cycle. Gene therapy has progressed a compelling therapeutic approach for various neurodegenerative disorders. Several efforts gene rely on discovering novel vectors, recent curative targets, dependability transgenic delivery paths. These viral non-viral vectors techniques are carefully screened through preclinical clinical levels eventually render patients with effective therapies. This review addresses developments obstacles diseases discusses emerging strategies, goals, prospects.

Язык: Английский

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LncRNA GAS5 and miR-137 Polymorphisms and Expression are Associated with Multiple Sclerosis Risk: Mechanistic Insights and Potential Clinical Impact

ACS Chemical Neuroscience, Год журнала: 2020, Номер 11(11), С. 1651 - 1660

Опубликована: Апрель 29, 2020

The pathogenesis of multiple sclerosis (MS) is influenced by the interaction genetic and epigenetic mechanisms. long noncoding RNA GAS5 acts as a competing endogenous for microRNA-137 involved in demyelination. We investigated association miR-137 expression their polymorphisms with MS susceptibility. One hundred eight patients 104 healthy controls were included. Expression analysis genotyping GAS5-rs2067079 miR-137-rs1625579 single nucleotide performed qPCR. Serum was upregulated, while serum downregulated compared controls. an excellent discriminator from (AUC = 0.97) negative independent predictor multivariate logistic analysis. positively correlated expanded disability status scale scores relapsing-remitting patients. rs2067079TT minor homozygote genotype associated increased risk, rs1625579G allele protective. rs1625579 showed age-specific effect, rs2067079 affected risk gender- manners. In patients, higher than other genotypes, did not differ between genotypes. Our results suggest biomarkers, marker severity. propose novel markers susceptibility, at least, possibly impacts crosstalk miR-137.

Язык: Английский

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