Roles of HOTAIR Long Non-coding RNA in Gliomas and Other CNS Disorders

Cellular and Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 44(1)

Published: Feb. 16, 2024

Abstract HOX transcript antisense intergenic RNA ( HOTAIR ) is a long non-coding (lncRNA) which increasingly being perceived as tremendous molecular mediator of brain pathophysiology at multiple levels. Epigenetic regulation target gene expression carried out by thorough modulation chromatin modifiers; histone methyltransferase polycomb repressive complex 2 (PRC2) and demethylase lysine-specific 1 (LSD1). Incidentally, was the first lncRNA shown to elicit sponging specific microRNA (miRNA or miR) species in trans-acting manner. It has been extensively studied various cancers, including gliomas regarded prominent pro-tumorigenic pro-oncogenic lncRNA. Indeed, may serve glioma grade predictor prognostic biomarker. The objective this timely review not only outline multifaceted pathogenic roles development but also delineate research findings implicating it critical regulator overall pathophysiology. While major focus on neuro-oncology, wherein represents particularly potent underlying player suitable therapeutic target, mechanisms regulatory actions neurodegeneration, traumatic, hypoxic ischemic injuries, neuropsychiatric disorders are presented. Graphical HOTAIR-mediated epigenetic DNA miRNAs. 5′ end regulates H3K27 trimethylation activity catalytic subunit enhancer Zeste homolog (EZH2) (PRC2), its 3′ modulates H3K4 demethylation binds competitively inhibits functions miRNAs, altering downstream genes.

Language: Английский

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Natural antisense transcripts as versatile regulators of gene expression

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: April 17, 2024

Language: Английский

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Molecular hallmarks of ageing in amyotrophic lateral sclerosis

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: March 2, 2024

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal, severely debilitating and rapidly progressing disorder affecting motor neurons in the brain, brainstem, spinal cord. Unfortunately, there are few effective treatments, thus remains critical need to find novel interventions that can mitigate against its effects. Whilst aetiology of ALS unclear, ageing major risk factor. Ageing slowly progressive process marked by functional decline an organism over lifespan. However, it unclear how promotes ALS. At molecular cellular level specific hallmarks characteristic normal ageing. These highly inter-related overlap significantly with each other. Moreover, whilst process, striking similarities at between these factors neurodegeneration Nine were originally proposed: genomic instability, loss telomeres, senescence, epigenetic modifications, dysregulated nutrient sensing, proteostasis, mitochondrial dysfunction, stem cell exhaustion, altered inter-cellular communication. recently (2023) expanded include dysregulation autophagy, inflammation dysbiosis. Hence, given latest updates hallmarks, their close association disease processes ALS, new examination relationship pathophysiology warranted. In this review, we describe possible mechanisms which impacts on neurodegenerative implicated therapeutic may arise from this.

Language: Английский

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Editorial: Novel therapeutic target and drug discovery for neurological diseases, volume II

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

Published: Feb. 27, 2025

Article typeThe research topic "New Therapeutic Target and Drug Discovery for Neurological Disorders, Volume II" encompasses 32 articles contributed by 236 authors. This comprehensive collection presents a wide range of content, comprising 13 original articles, 10 review 3 systematic reviews, 1 mini-review, opinion, clinical trial, case report, brief study protocol. The overarching goal this is to enhance our comprehension prospective therapeutic targets the fundamental mechanisms underlying innovative molecular therapies neurological diseases, ultimately aiming expedite advancement novel treatment approaches.A concentrates on pathological potential drug in diseases. Neuronal death pathways, including ferroptosis, apoptosis, pyroptosis, necroptosis, autophagy, are critical components development diseases [Moujalled et al., 2021]. Jin al. highlight importance pharmacological inhibition ferroptosis as strategy epilepsy, grounded an exhaustive examination central role ferroptosis. Wang spotlight maintenance endoplasmic reticulum stress reduce dopaminergic neurons Parkinson's disease (PD) through modulation key molecules such protein kinase RNA-like ER (PERK), activating transcription factor 4 (ATF4), nucleus signaling (IRE1), 6 (ATF6). conducted Nakamura identified alterations axon terminals globus pallidus internus (GPi), characterized hypertrophy increased gamma-aminobutyric acid (GABA) release, caused levodopa treatment. work suggests that gabaergic neuromodulation could be target levodopainduced dyskinesia. Xu systematically elaborated neuroprotective Apelin/Apelin-receptor (APJ) system mitigating oxidative during stroke, highlighting its promise target. Beyond neurons, glial cells have received increasing attention pathogenesis Li utilized chronic restraint (CRS) mouse model explore how targeting microglia combat depression. They found reducing Discs large homolog (Dlg1) expression significantly decreased number activated microglia, leading improvement depression-like behavior. In another study, demonstrated astrocytes CRS-induced depression mice, indicating enhancing astrocyte energy metabolism mitochondrial phosphorylation contributes rapid antidepressant effect hypidone hydrochloride. Zhang explored nuclear erythroid 2-related 2 (Nrf2)antioxidant response element (ARE) signal transducer activator (STAT3)inhibitor kappa B (NF-κB) zeta (IκBζ) pathways multiple sclerosis with dimethyl fumarate. Moreover, recent studies emphasize crucial epigenetics, particularly noncoding RNAs, [Li 2021;Srinivas 2023;Zeng 2025 and2021;Zhao 2024]. subject area, microRNA-23b-3p (miR-23b-3p) Alzheimer's (AD) prospects illustrate miR-23b-3p alleviates cognitive deficits APPswe/PSEN1dE9 (APP/PS1) mice regulating glycogen synthase kinase-3 beta (GSK-3β)/ phosphatase tensin (PTEN)/ phosphorylated tau (p-Tau)/ BCL2 associated X-protein (Bax)/Caspase-3 neurons. Additionally, they small capable systems acting miR-23b-3p-mediated presenting inventive approach AD. Another focus RNA-binding proteins, quaking (QKI), which responsible RNA generation messenger (mRNA) splicing. Guo provide detailed overview QKI nervous suggest new treating axial gliomas preserving stemness glioblastoma multiforme (GBM) tumor microenvironment. Protein modifications, palmitoylation, serve elements pathology dysfunction, modifying function localization addition palmitate chains [He 2023]. Liao thoroughly studied zinc finger DHHC-type (zDHHC) proteins brain, proposing zDHHC palmitoylation disorders.Another group delves into application molecule drugs, peptide natural products, traditional Chinese medicine (TCM) Feng reported findings NH300094, compound, efficacy schizophrenia impairment due 5hydroxytryptamine receptor 2A (5-HT2A) antagonist activity antagonism dopamine D2 D3 receptors. Meanwhile, two teams focused drugs against neuronal injuries. Gao investigated effects AV-001 elderly female rats vascular dementia (VaD) microinfarcts (MMI), revealing angiopoietin-1 mimicking polypeptide mitigated white matter (WM) damage improved neurocognitive function. Alternatively, Xiong showed parathyroid hormone analogue teriparatide outcome spinal cord injury (SCI) blood-spinal barrier disruption. Natural products arisen pivotal sources (CNS) disorders [Appendino 2014] . illustrated herbal ingredients exhibited protecting via promotion neurotrophic secretion, brain-derived (BDNF), cell-derived (GDNF), endothelial growth (VEGF), nerve (NGF). Lu revealed Astragalus polysaccharides inhibited pentylenetetrazole-induced neuroinflammation thereby influencing occurrence epilepsy alleviating impairment. Du Rannasangpei, Tibetan medicine, active component Crocin-1, ameliorated unpredictable mild (CUMS)-induced depressive behavior inhibiting stress, inflammatory responses, apoptotic pathways. Dong Jingqianshu granules, containing peony page, Ligusticum essential oil, glycyrrhizin, hesperidin, paeonol, alleviated premenstrual symptoms modulating orexin pathway. addition, current pays particular both safety indication expansion existing drugs. Leu presented phase I intravenous nipocalimab administration 40 participants, favorable pharmacodynamic pharmacokinetic properties, suggesting effective immunoglobulin G (IgG)-mediated demyelinating polyradiculoneuropathy (CIDP). Zou posterior reversible encephalopathy syndrome (PRES) anlotinib summarized 54 PRES cases antiangiogenic agents, need early detection Through preclinical studies, analyzed challenges ketamine research, underscoring safety, resistance, long-term abuse risk priorities future research. meta-analysis covering 19 312 evaluated post-stroke (PSCI). indicated interventions, angiotensinconverting enzyme inhibitors, N-methyl-D-aspartate (NMDAR) antagonists, cell therapy, acupuncture, Western combined ginkgo biloba extract (EGB761), improving activities daily living, while also demonstrating profiles. repurposing important therapeutics [Ballard 2020]. Cui metformin can employed appraised efficacy, medication initiates pathway insulin resistance providing protection. Chen proposed multicenter, double-blind, randomized controlled trial (PSSH) regarding spontaneous subarachnoid hemorrhage (SAH) pioglitazone. meticulously designed protocol, their aimed evaluate profile pioglitazone, offering high-quality evidence support SAH.The final series discusses advanced technologies tailored discovery biomarkers field TCM treasure trove initiatives. Gong used patch-clamp methodologies screen compounds wild guava (TSS), uncovering triterpene saponins C9 C10 analgesic transient vanilloid (TRPV1) channels dorsal root ganglion (DRG) Furthermore, these suppressed inhibitory synaptic signaling, concurrent upregulation GABA receptors (GABAA) cortical network analysis experimental verification, four core ten Erjingwan decoction AD, hinting at glycation end (AGEs)/ AGEs (RAGE)/NF-κB mechanism efficacy. Fan constructed fluorescence resonance transfer (FRET)-based probe measure intermediate filament tension screened complex nanoparticles (PNs) sodium/chloride channel inhibitors evaluating intracellular osmotic potential. Their results effectiveness astrocyte-induced brain edema toxicity within rat middle cerebral artery occlusion (MCAO). Tang integrated metabolomics bioinformatics techniques reveal regulatory Mogroside V (MGV) metabolite Mogrol (MG) 106 metabolites substantia nigra 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. MGV MG modulated metabolic sphingolipid metabolism, fatty amino theoretical basis understanding Siraitia grosvenorii (Swingle) C. Jeffrey PD. Cai restores disrupted RNA-mediated improve neurodegenerative fresh perspective regulation multi-stage RNA-associated TCM. discussed strategies intracranial delivery preparations across blood-brain barrier, path translation from laboratory applications. realm biomarker discovery, Bian marker, tryptophan indoleacrylic acid, anti-inflammatory liquid chromatography-tandem mass spectrometry (LC-MS/MS) cerebrospinal fluid serum patients neuromyelitis optica spectrum (NMOSD). performed scientometric pertaining NMDAR context investigating action antagonists identifying areas therapies. Yang compare different extracellular vesicles (EVs) traumatic (TBI), concluding astrocyte-derived EVs (AEVs) mesenchymal stem (MSC-EVs) most promising TBI finding provides ideas therapies.In summary, covers diverse endeavors, valuable insights Studies centered epigenetic neuroimmunological broadened horizon disorders. cutting-edge multi-omics aiding targets. elucidating TCM, alongside repurposing, developing treatments intricate conditions. We acknowledge significant contributions editorial team, authors, reviewers Frontiers Pharmacology.

Language: Английский

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Deciphering the epigenetic role of long non‐coding RNAs in mood disorders: Focus on human brain studies

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

Language: Английский

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Phytochemicals Modulate Biosynthesis and Function of Serotonin, Dopamine, and Norepinephrine for Treatment of Monoamine Neurotransmission-Related Psychiatric Diseases

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2916 - 2916

Published: March 23, 2025

Serotonin (5-HT), dopamine (DA), and norepinephrine (NE) are key monoamine neurotransmitters regulating behaviors, mood, cognition. 5-HT affects early brain development, its dysfunction induces vulnerability to stress, raising the risk of depression, anxiety, autism in adulthood. These synthesized from tryptophan tyrosine via hydroxylation decarboxylation, metabolized by oxidase (MAO). This review aims summarize current findings on role dietary phytochemicals modulating neurotransmitter biosynthesis, metabolism, function, with an emphasis their potential therapeutic applications neuropsychiatric disorders. Phytochemicals exert antioxidant, neurotrophic, neurohormonal activities, regulate gene expression, induce epigenetic modifications. Phytoestrogens activate estrogen receptors or estrogen-responsive elements promoter target genes, enhance transcription hydroxylase hydroxylase, while inhibiting that MAO. compounds also influence interaction between genetic environmental factors, potentially reversing dysregulated neurotransmission architecture associated conditions. Despite promising preclinical findings, clinical remain challenging. Advances nanotechnology targeted delivery systems offer solutions efficacy. discusses mechanisms, challenges, strategies, underscoring need for further research advance phytochemical-based interventions diseases.

Language: Английский

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The Role of Hydrogen Sulfide (H2S) in Epigenetic Regulation of Neurodegenerative Diseases: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12555 - 12555

Published: Aug. 8, 2023

This review explores the emerging role of hydrogen sulfide (H

Language: Английский

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Divergent patterns of healthy aging across human brain regions at single-cell resolution reveal links to neurodegenerative disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 1, 2023

Abstract Age is a major common risk factor underlying neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s and amyotrophic lateral sclerosis. Previous studies reported that chronological age correlates with differential gene expression across different brain regions. However, prior datasets have not disambiguated whether associations are due to changes in cell numbers and/or per cell. In this study, we leveraged single nucleus RNA-sequencing (snRNAseq) examine proportions transcriptomes four regions, each from 12 donors aged 20-30 years (young) or 60-85 (old). We sampled 155,192 nuclei two cortical regions (entorhinal cortex middle temporal gyrus) subcortical (putamen subventricular zone) relevant diseases the proliferative niche. found no cellular composition of healthy aging. Surprisingly, did find region has distinct aging signature, only minor overlap differentially associated genes Moreover, type shows age-associated changes, loss protein synthesis inhibitory neurons, axonogenesis excitatory neurons oligodendrocyte precursor cells, enhanced gliosis markers astrocytes disease-associated microglia, critical for neuron-glia communication. Importantly, type-specific enrichments nominated by disease genome-wide association (GWAS), such as apolipoprotein E ( APOE ), leucine-rich repeat kinase 2 LRRK2 ) microglia independent overall levels types. present data new resource which highlights, first, region- transcriptomic may contribute selective vulnerability and, second, provide context testing GWAS-nominated subtypes developing more targeted therapeutic strategies. The readily accessible without requirement extensive computational support public website, https://brainexp-hykyffa56a-uc.a.run.app/ Graphical *Created using Biorender.com Highlights Establishment atlas human Each exhibits unique aging-associated transcriptome signature Gene occur absence overt categorically types Neurological patterns specific

Language: Английский

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Techniques for investigating lncRNA transcript functions in neurodevelopment

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 29(4), P. 874 - 890

Published: Dec. 25, 2023

Long noncoding RNAs (lncRNAs) are sequences of 200 nucleotides or more that transcribed from a large portion the mammalian genome. While hypothesized to have variety biological roles, many lncRNAs remain largely functionally uncharacterized due unique challenges associated with their investigation. For example, some overlap other genomic loci, expressed in cell-type-specific manner, and/or differentially processed at post-transcriptional level. The CNS contains vast diversity lncRNAs, and highly abundant brain. However, interrogating lncRNA function models CNS, particularly vivo, can be complex challenging. Here we review breadth methods used investigate merits, understanding they provide respect neurodevelopment pathophysiology. We discuss remaining field recommendations assay based on current methods.

Language: Английский

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Biomarkers in neurodegenerative diseases: a broad overview

Exploration of Neuroprotective Therapy, Journal Year: 2024, Volume and Issue: unknown, P. 119 - 147

Published: April 16, 2024

Degeneration and dysfunction of neurons in the brain are hallmarks neurodegenerative diseases. Over past decades, significant efforts have been devoted to development validation biomarkers for The range diversity central nervous system (CNS) diseases has continued expand, encompassing biofluid-based sources such as blood or cerebrospinal fluid (CSF), nucleic acids, tissues, imaging. While imaging tissue biopsy-based markers continually being identified their applications expanding, they do limitations compared with RNA protein biomarkers. This review comprehensively summarizes various biomarkers, including microRNA (miRNA), long noncoding (lncRNA), circulating miRNA (cimiRNA), proteins, context CNS disorders. In addition, emphasizes existing challenges associated use both clinical practice research on conclusion, this provides an insightful overview diseases, underscoring crucial role biomarker combating these debilitating conditions. article also highlights future related implementation novel trials, thereby contributing ongoing advance understanding management

Language: Английский

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