N-methyladenosine modification in ischemic stroke: Functions, regulation, and therapeutic potential

Heliyon, Journal Year: 2024, Volume and Issue: 10(3), P. e25192 - e25192

Published: Jan. 23, 2024

N6-methyladenosine (m6A) modification is the most frequently occurring internal in eukaryotic RNAs. By modulating various aspects of RNA life cycle, it has been implicated a wide range pathological and physiological processes associated with human diseases. Ischemic stroke major cause death disability worldwide few treatment options narrow therapeutic window, accumulating evidence indicated involvement m6A modifications development progression this type stroke. In review, which provides insights for prevention clinical stroke, we present an overview roles played by ischemic from three main perspectives: (1) association established risk factors including hypertension, diabetes mellitus, hyperlipidemia, obesity, heart disease; (2) regulators their functional regulation pathophysiological injury mechanisms namely oxidative stress, mitochondrial dysfunction, endothelial neuroinflammation, cell processes; (3) diagnostic potential

Language: Английский

---

Circulating blood circular RNA in Parkinson’s Disease; a systematic study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 23, 2024

We aimed to identify circRNAs associated with Parkinson's disease (PD) by leveraging 1,848 participants and 1,789 circRNA from two of the largest publicly available studies longitudinal clinical blood transcriptomic data. To comprehensively understand changes in we performed a cross-sectional study utilizing last visit each participant, (mix model) analysis that included 1,166 at least time points. identified 192 differentially expressed PD compared healthy controls, effects were consistent mixed models, mutation carriers, diverse ancestry. Finally, 149 model ROC AUC 0.825, showing have potential aid diagnosis PD. Overall, demonstrated play an important role can be leveraged as biomarkers.

Language: Английский

---

Investigating the Epigenetic Landscape of Major Depressive Disorder: A Genome-Wide Meta-Analysis of DNA Methylation Data, including New Insights into Stochastic Epigenetic Muta-Tions and Epivariations

Published: Aug. 21, 2024

Major depressive disorder (MDD) is a prevalent mental health condition with substantial social and economic consequences. This study focuses on the interplay between genetic environmen-tal factors in MDD, particular emphasis epigenetic mechanisms such as stochastic epige-netic mutations (SEMs), age acceleration, drift. We conducted meta-analysis of DNA methylation patterns across six datasets (n=1125 MDD cases, 398 controls whole blood; n=95 96 brain tissues) from Gene Expression Omnibus. The analysis did not reveal significant global differences cases controls. However, brain-specific probe (cg25801113) near SHF gene consistently exhibited hypomethylation, suggesting its potential relevance to MDD. SEMs were assessed, revealing dis-tinct burden at level though no findings emerged for indicating it may play central role also identified rare epivariations specific genes unique cases. In blood tissue, 51 associated these epivariations, while 1 was highlighted tissue. These results un-derscore importance exploring understanding molecular mecha-nisms underlying offer targets further investigation.

Language: Английский

---

Brain-Region-Specific Differences in Protein Citrullination/Deimination in a Pre-Motor Parkinson’s Disease Rat Model

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(20), P. 11168 - 11168

Published: Oct. 17, 2024

The detection of early molecular mechanisms and potential biomarkers in Parkinson’s disease (PD) remains a challenge. Recent research has pointed to novel roles for post-translational citrullination/deimination caused by peptidylarginine deiminases (PADs), family calcium-activated enzymes, the stages disease. current study assessed brain-region-specific citrullinated protein targets their associated protein–protein interaction networks alongside PAD isozymes 6-hydroxydopamine (6-OHDA) induced rat model pre-motor PD. Six brain regions (cortex, hippocampus, striatum, midbrain, cerebellum olfactory bulb) were compared between controls/shams PD model. For all regions, there was significant difference IDs controls. Citrullinated hits most abundant cortex followed cerebellum, bulb striatum. Citrullinome-associated pathway enrichment analysis showed correspondingly considerable differences six regions; some overlapping controls PD, identified only, control brains only. KEGG (Kyoto Encyclopedia Genes Genomes) pathways only with neurological, metabolic, immune hormonal functions included following: “Axon guidance”; “Spinocerebellar ataxia”; “Hippo signalling pathway”; “NOD-like receptor “Phosphatidylinositol system”; “Rap1 “Platelet activation”; “Yersinia infection”; “Fc gamma R-mediated phagocytosis”; “Human cytomegalovirus “Inositol phosphate metabolism”; “Thyroid hormone “Progesterone-mediated oocyte maturation”; “Oocyte meiosis”; “Choline metabolism cancer”. Some furthermore observed five (PADs 1, 2, 3, 4 6), changes 3 when comparing regions. Our findings indicate that PAD-mediated citrullination plays immune, cell neurodegenerative disease-related across highlighting PADs as future therapeutic avenues.

Language: Английский

---

Polymorphism in Genes Encoding HSP40 Family Proteins is Associated with Ischemic Stroke Risk and Brain Infarct Size: A Pilot Study

Journal of Integrative Neuroscience, Journal Year: 2024, Volume and Issue: 23(12)

Published: Dec. 4, 2024

Background: Heat shock proteins (HSPs) play a critical role in the molecular mechanisms of ischemic stroke (IS). A possible for HSP40 family atherosclerosis progression has already been revealed; however, to date, genetic studies on involvement genes encoding IS have not yet carried out. Aim: We sought determine whether nine single nucleotide polymorphisms (SNPs) (DNAJB1, DNAJB2, DNAJA1, DNAJA2, DNAJA3 and DNAJC7) are associated with risk clinical features IS. Methods: Using TaqMan-based polymerase chain reaction (PCR) MassArray-4 system, DNA samples 2551 Russians — 1306 patients 1245 healthy individuals were genotyped. Results: SNP rs2034598 DNAJA2 decreased exclusively male (odds ratio = 0.81, 95% confidence interval 0.78–0.98, p 0.028); rs7189628 increased brain infarct size (p 0.04); rs6500605 lowered age onset 0.03). SNPs rs10448231 rs4926222 DNAJB1 involved strongest epistatic interactions linked IS; DNAJA1 is characterised by most essential mono-effect (2.96% entropy); all top SNP–SNP interaction models included pairwise combination DNAJA2×rs4926222 DNAJB1, which was found be key factor determining susceptibility In studied SNPs, smoking multidirectional effects (synergism, antagonism or additive effect) (3.47% entropy), exceeding mono-effects DNAJA3, best G×E 0.03%–0.73% entropy. Conclusions: first discover as major its manifestations. The comprehensive bioinformatics analysis revealed mechanisms, underscoring their significance pathogenesis IS, primarily reflecting regulation heat stress, proteostasis cellular signalling.

Language: Английский

---

Human Nasal Inferior Turbinate-Derived Neural Stem Cells Improve the Niche of Substantia Nigra Par Compacta in a Parkinson’s Disease Model by Modulating Hippo Signaling

Tissue Engineering and Regenerative Medicine, Journal Year: 2024, Volume and Issue: 21(5), P. 737 - 748

Published: April 10, 2024

Abstract Background: Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases, following Alzheimer’s disease. The onset PD characterized by loss dopaminergic neurons in substantia nigra. Stem cell therapy has great potential for treatment and human nasal turbinate-derived stem cells (hNTSCs) have been found to share some characteristics with mesenchymal cells. Although Hippo signaling pathway was originally thought regulate size organs, recent studies shown that it can also control inflammation neural Methods: Dopaminergic neuron-like were differentiated from SH-SY5Y (DA-Like cells) treated 1-Methyl-4-phenylpyridinium iodide stimulate Reactive oxidative species (ROS) production. A transwell assay conducted validate effect hNTSCs on pathway. We generated an MPTP-induced mouse model transplanted into nigra mice via stereotaxic surgery. After five weeks behavioral testing, brain samples validated immunoblotting immunostaining confirm niche hNTSCs. Results: In-vitro experiments showed significantly increased survival exerted anti-inflammatory effects controlling ROS-mediated ER stress hippocampal factors . Similarly, in-vivo demonstrated increase rate. transplantation hNTSCs, improved mobility relief symptoms. Conclusion: rate manipulating through Yes-associated protein (YAP)/transcriptional coactivator a PDZ-binding motif (TAZ) reducing inflammatory cytokines. In this study, we had therapeutic lesions.

Language: Английский

---

Synaptic gene expression changes in frontotemporal dementia due to the MAPT 10 + 16 mutation

Neuropathology and Applied Neurobiology, Journal Year: 2024, Volume and Issue: 50(4)

Published: Aug. 1, 2024

Mutations in the MAPT gene encoding tau protein can cause autosomal dominant neurodegenerative tauopathies including frontotemporal dementia (often with Parkinsonism). In Alzheimer's disease, most common tauopathy, synapse loss is strongest pathological correlate of cognitive decline. Recently, Positron Emission Tomography (PET) imaging synaptic tracers revealed clinically relevant synapses primary tauopathies; however, molecular mechanisms leading to degeneration remain largely unknown. this study, we examined post-mortem brain tissue from people who died pathology (FTDtau) caused by intronic exon 10 + 16 mutation, which increases splice variants containing resulting higher levels four microtubule-binding domains.

Language: Английский

---

Investigating the Epigenetic Landscape of Major Depressive Disorder: A Genome-Wide Meta-Analysis of DNA Methylation Data, Including New Insights into Stochastic Epigenetic Mutations and Epivariations

Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2181 - 2181

Published: Sept. 25, 2024

Major depressive disorder (MDD) is a mental health condition that can severely impact patients' social lives, leading to withdrawal and difficulty in maintaining relationships. Environmental factors such as trauma stress worsen MDD by interacting with genetic predispositions. Epigenetics, which examines changes gene expression influenced the environment, may help identify patterns linked depression. This study aimed explore epigenetic mechanisms behind analysing six public datasets (n = 1125 cases, 398 controls blood; n 95 96 brain tissues) from Gene Expression Omnibus.

Language: Английский

---

Mechanism of action of “cistanche deserticola–Polygala” in treating Alzheimer's disease based on network pharmacology methods and molecular docking analysis

IET Systems Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 11, 2024

Abstract This article used network pharmacology, molecular docking, GEO analysis, and Gene Set Enrichment Analysis to obtain 38 main chemical components 66 corresponding targets involved in Alzheimer's disease (AD) treatment "Cistanche deserticola‐Polygala". Through further Ontology Kyoto Encyclopaedia of Genes Genomes enrichment we obtained AD signalling pathways, calcium other pathways related the with “Cistanche deserticola‐Polygala”. Molecular docking showed that most core had good binding ability targets. aims reveal mechanism deserticola‐Polygala” treating provide a basis for

Language: Английский

---

Hippo-vgll3 signaling may contribute to sex differences in Atlantic salmon maturation age via contrasting adipose dynamics

Published: Oct. 24, 2024

Abstract Sexual maturation in Atlantic salmon entails a transition energy utilization, governed part by genes and environmental stimuli sex-specific manner. Salmon males require less energy, the form of adiposity, to mature compared females typically younger. Maturation age is also influenced sex-dependent fashion vgll3 genotype ( vestigial-like 3 ), co-factor Hippo pathway. The underlying molecular processes age, how they interplay with adiposity genotypes, have remained unknown. To elucidate mechanisms sex- genotype-specific differences, we investigated association early (E) late (L) alleles transcriptional expression > 330 involved regulation pathway sexual maturation, related signals brain, adipose tissue, gonads. strongest effect was observed tissue for brain males, highlighting difference main genotype. Genes ovarian development showed increased vgll3*EE vgll3*LL females. Additionally, exhibited reduced markers pre-adipocyte differentiation lipolysis yet enhanced adipocyte lipid storage. Brain gene further hormones lipids, as well tight junction assembly. Overall, these patterns point towards greater storage slower utilization males. These results suggest that Hippo-dependent may be important mediators sex differences salmon.

Language: Английский

---