miRNAs in neurodegenerative diseases: from target screening to precision therapy

Neurological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Language: Английский

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RNA and condensates: Disease implications and therapeutic opportunities

Cell chemical biology, Journal Year: 2024, Volume and Issue: 31(9), P. 1593 - 1609

Published: Sept. 1, 2024

Language: Английский

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MicroRNAs regulation in Parkinson’s disease, and their potential role as diagnostic and therapeutic targets

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Oct. 5, 2024

Language: Английский

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In Silico Analysis of miRNA-Regulated Pathways in Spinocerebellar Ataxia Type 7

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(3), P. 170 - 170

Published: March 2, 2025

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease characterized by cerebellar and retinal degeneration, caused abnormal expansion of the CAG trinucleotide in coding region ATXN7 gene. Currently, silico analysis used to explore mechanisms biological processes through bioinformatics predictions various diseases. Therefore, aim this study was identify candidate human gene targets four miRNAs (hsa-miR-29a-3p, hsa-miR-132-3p, hsa-miR-25-3p, hsa-miR-92a-3p) involved pathways that could play important role SCA7 pathogenesis comprehensive including prediction miRNA target genes, Gen Ontology enrichment, identification core genes KEGG pathways, transcription factors validated with mouse transcriptome data. Our results showed participation following pathways: adherens junction, focal adhesion, neurotrophin signaling, endoplasmic reticulum processing, actin cytoskeleton regulation, RNA transport, apoptosis dopaminergic synapse. In conclusion, unlike previous studies, we highlight using a approach different which ones are for miRNAs, which, addition being associated diseases, also de-regulated plasma patients SCA7.

Language: Английский

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Exosomes enriched with miR-124-3p show therapeutic potential in a new microfluidic triculture model that recapitulates neuron–glia crosstalk in Alzheimer’s disease

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 12, 2025

Background Alzheimer’s disease (AD), a complex neurodegenerative associated with ageing, is the leading cause of dementia. Few people early AD are eligible for novel Food and Drug Administration (FDA)-approved drug treatments. Accordingly, new tools diagnosis markers required to predict subtypes, individual stages, most suitable personalized treatment. We previously demonstrated that regulation microRNA (miR)-124 crucial proper neuronal function microglia reshaping in human cell models. Objective The aim this study was develop an efficient miR-124-3p-loaded exosome strategy validate its therapeutic potential using multi-compartment microfluidic device neuron–glia recapitulates age-AD pathological features. Methods results Using cortical from mouse pups, separated glial mixed cultures maintained 2 days vitro (stressed microglia), we tested effects SH-SY5Y-derived exosomes loaded miR-124-3p mimic either by their direct transfection Exo-Fect™ (ET124) or isolation secretome miR-124 transfected cells (CT124). ET124 revealed better delivery effciency higher potent improving stressed status than CT124. Tricultures SH-SY5Y neuroblastoma (SH- WT ) were established presence line (HMC3) immortalized astrocytes (IM-HA) tricompartmentalized devices. Replacement SH- those APP695 SWE tricultures addition low doses hydrogen peroxide used simulate late-onset AD. system mimicked AD-associated neurodegeneration neuroinflammation processes. Notably, exhibited neuroprotective properties across three types model preventing apoptosis neurite deficits, redirecting microglial profiles towards steady state, attenuating inflammatory miRNA fingerprints astrocyte reactivity. Conclusion To best our knowledge, first supporting neuro- immunoprotective miR-124-engineered triculture platform, recapitulating age-related susceptibility Our offers medicines patient subtypes.

Language: Английский

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The role of retroelements in Parkinson’s disease development

Vavilov Journal of Genetics and Breeding, Journal Year: 2025, Volume and Issue: 29(2), P. 290 - 300

Published: April 11, 2025

Parkinson’s disease is the second most common neurodegenerative characterized by accumulation of alpha-synuclein and Lewy bodies in brain’s substantia nigra. Genetic studies indicate an association various SNPs, many which are located intergenic intronic regions, where retrotransposons non-coding RNA genes derived from them reside, with this disease. Therefore, we hypothesize influence SNPs retroelement on development. A susceptibility factor activation age, since associated aging. We hypothesized that accumulates brain due to its interaction transcripts activated retroelements. As a result defective antiviral response large number targets for protein, aggregates form neurons inflammation neurodegeneration development evidence, data presented role binding viruses, ability activate retroelements have evolved exogenous viruses integrated into human genome. Activation LINE1s brain, endogenous retroviruses, blood serum patients was detected. An additional mechanism contributing progression mitochondrial dysfunction insertions Alu elements their genomes using LINE1 enzymes. Mechanisms retrotransposons’ microRNAs described. Analysis scientific literature allowed us identify 35 such (miR-1246, -1249, -1271, -1273, -1303, -151, -211, -28, -31, -320b, -320d, -330, -335, - 342, -374a, -374b, -421, -4293, -4317, -450b, -466, -487b, -493, -495, -5095, -520d, -576, -585, -6088, -619, -625, -626, -769, -885, -95) disease, may become promising treatment diagnosis.

Language: Английский

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MiR-27a-3p protects against NaAsO2-induced neuronal apoptosis in HT22 cells

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 23, 2025

Environmental arsenic exposure is closely related to nerve damage. Recent research suggests miR-27a-3p involved in the development of certain neurodegenerative and neuropsychiatric diseases. Nonetheless, precise impact on neuron functioning hippocampus remains unclear. In this investigation, models were established using NaAsO2-treated mice cells investigate aspect. Male C57BL/6J given drinking water containing sodium arsenite (0, 0.5, 5, or 50 ppm) for 48 weeks. The results showed that induced apoptosis mouse neurons. After 6 μmol/L treatment HT22 cells, expression level was decreased, FTO, DRP1 p-DRP1 (Ser616), neuronal pro-apoptotic proteins (Bax cleaved asparaginase 3) increased, anti-apoptosis Bcl-2 MMP which indicated could activate FTO/DRP1 pathway. Furthermore process be reversed by mimics. This study demonstrates alleviates arsenite-induced mitochondrial dysfunction inhibiting provides a scientific basis finding early biomarkers control arsenic-induced neurotoxicity discovering new prevention measures.

Language: Английский

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MicroRNAs Modulating Neuroinflammation in Parkinson's disease

Inflammation, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 20, 2024

Language: Английский

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Insights into the Role of microRNAs as Clinical Tools for Diagnosis, Prognosis, and as Therapeutic Targets in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9936 - 9936

Published: Sept. 14, 2024

Neurodegenerative diseases (NDDs) are a diverse group of neurological disorders characterized by alterations in the structure and function central nervous system. Alzheimer’s disease (AD), impaired memory cognitive abilities, is most prevalent type senile dementia. Loss synapses, intracellular aggregation hyperphosphorylated tau protein, extracellular amyloid-β peptide (Aβ) plaques hallmarks AD. MicroRNAs (miRNAs/miRs) single-stranded ribonucleic acid (RNA) molecules that bind to 3′ 5′ untranslated regions target genes cause post-transcriptional gene silencing. The brain expresses over 70% all experimentally detected miRNAs, these miRNAs crucial for synaptic particular signals during formation. Increasing evidence suggests play role AD pathogenesis we provide an overview synapse formation, Aβ synthesis, protein accumulation, brain-derived neurotrophic factor-associated pathogenesis. We further summarize discuss as potential therapeutic targets biomarkers detection differentiation between early- late-stage AD, based on recent research. In conclusion, altered expression peripheral circulation demonstrates their

Language: Английский

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Upregulation of microRNAs correlates with downregulation of HERV-K expression in Parkinson’s disease

Journal of NeuroVirology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 18, 2024

Abstract Human endogenous retroviruses (HERVs) involvement in neurological diseases has been extensively documented, although the etiology of HERV reactivation remains unclear. MicroRNAs represent one potential regulatory mechanisms reactivation. We identified fourteen microRNAs predicted to bind HERV-K transcript, and subsequently analyzed for their gene expression levels alongside those HERV-K. documented an increased four patients with Parkinson’s disease compared healthy controls, which correlated a downregulation transcripts. hypothesize that specific may transcripts, leading its downregulation.

Language: Английский

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