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МикроРНК-219 в центральной нервной системе: потенциальный тераностический подход.

Несмотря на недавние терапевтические достижения в области неврологических расстройств, лечебная терапия во многих случаях остается серьезной проблемой. Несмотря на то, что в последние годы мы стали свидетелями развития генной терапии из различных терапевтических подходов, влияющих на патофизиологические механизмы, существуют интригующие аспекты, касающиеся эффективности, безопасности и механизма действий генной терапии. Микрорибонуклеиновая кислота (микроRNA-miRNA) в качестве основного генного регулятора регулирует рибонуклеиновую кислоту курьера (mRNA) путем прямого соединения через 3'неперев

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… Evaluation of miR-219 in the whole brain tissue and synaptosomes revealed that miR-219-3p and miR-219-5p were upregulated in the whole tissue, but downregulated in the cortical synaptosomes of schizophrenic patients ( 79 80 ). NMDA receptors suppress miR-219 and its disinhibition effect on CAMKIIγ. …

Deciphering transcriptomic changes in chemobrain: a comprehensive review.

Chemotherapy-induced cognitive impairments (CICI), colloquially known as "chemobrain," represents a profound and debilitating side effect experienced by a significant number of cancer survivors, impacting their memory, multitasking, and quality of life. This review critically evaluates the molecular mechanisms underlying CICI, with a particular focus on the insights gained from transcriptomic analyses. As cancer incidence rises globally, understanding the complex interplay between chemotherapy agents and their cognitive repercussions becomes increasingly vital. Key mechanisms implicated in CIC

Role for Reelin in neurotransmitter release.

The extracellular matrix molecule Reelin is known to control neuronal migration during development. Recent evidence suggests that it also plays a role in the maturation of postsynaptic dendrites and spines as well as in synaptic plasticity. Here, we aimed to address the question whether Reelin plays a role in presynaptic structural organization and function. Quantitative electron microscopic analysis of the number of presynaptic boutons in the stratum radiatum of hippocampal region CA1 did not reveal differences between wild-type animals and Reelin-deficient reeler mutant mice. However, additi

Идентификация диагностических микроРНК и их целевых генов в множестве склерозов на основе взаимодействия сетей с использованием силико-подхода.

Фон: Наиболее распространенным демиелинизирующим заболеванием нервных волокон в мозгу и спинном мозге является множественный склероз (MS), который связан с несколькими нарушениями. Ранняя диагностика и лечение MS могут замедлить развитие инвалидности. С этой целью наше исследование направлено на выявление диагностических микрорибонуклеиновых кислот (miRNA) и их целевых генов в MS. Методы: Для выявления регулируемых и дерегулированных генов и миРНС у пациентов с MS, GSE17846 (платформа: GPL9040, 20 образцов MS и 21 контрольный образец), GSE108000 (платформа: GPL 570, 7 хронических активных пора

Терапевтическая ориентация на нейроинфламацию, вызванную ожирением, и нейродегенерацию.

Ожирение является одним из основных из изменяемых факторов риска, ведущих к нейроинфламмации и нейродегенерации. Чрезмерное содержание жира в ожирении способствует постепенному проникновению иммунных клеток в жировые ткани, что приводит к высвобождению провоспалительных факторов, таких, как цитокины и адипокины. Эти подстрекательские посредники циркулируют по кровотоку, пропагандируя воспаление как на периферии, так и в центральной нервной системе. Гут дисбиоз, который приводит к утечке кишечного барьера, усугубляет воспаление и играет важную роль в увязке ожирения с патогенезом нейроинфламмац

The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines.

NMDA-type glutamate receptors play a critical role in the activity-dependent development and structural remodeling of dendritic arbors and spines. However, the molecular mechanisms that link NMDA receptor activation to changes in dendritic morphology remain unclear. We report that the Rac1-GEF Tiam1 is present in dendrites and spines and is required for their development. Tiam1 interacts with the NMDA receptor and is phosphorylated in a calcium-dependent manner in response to NMDA receptor stimulation. Blockade of Tiam1 function with RNAi and dominant interfering mutants of Tiam1 suggests that

Tumor microenvironment and exosomes in brain metastasis: Molecular mechanisms and clinical application.

Metastasis is one of the important biological features of malignant tumors and one of the main factors responsible for poor prognosis. Although the widespread application of newer clinical technologies and their continuous development have significantly improved survival in patients with brain metastases, there is no uniform standard of care. More effective therapeutic measures are therefore needed to improve prognosis. Understanding the mechanisms of tumor cell colonization, growth, and invasion in the central nervous system is of particular importance for the prevention and treatment of brai

The emerging role of exosomes in innate immunity, diagnosis and therapy.

Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exo

An Appraisal of the Oleocanthal-Rich Extra Virgin Olive Oil (EVOO) and Its Potential Anticancer and Neuroprotective Properties.

Dietary consumption of olive oil represents a key pillar of the Mediterranean diet, which has been shown to exert beneficial effects on human health, such as the prevention of chronic non-communicable diseases like cancers and neurodegenerative diseases, among others. These health benefits are partly mediated by the high-quality extra virgin olive oil (EVOO), which is produced mostly in Mediterranean countries and is directly made from olives, the fruit of the olive tree (Olea europaea L.). Preclinical evidence supports the existence of antioxidant and anti-inflammatory properties exerted by t

От ожирения до митохондриальной дисфункции в периферальных тканях и в центральной нервной системе.

Ожирение - это состояние хронического низкосортного воспаления, затрагивающего периферийные органы тела, а также центральную нервную систему. Дефункция жировой ткани, возникающая в условиях ожирения, является ключевым фактором возникновения и развития различных заболеваний, включая нейродегенеративные расстройства. Митохондрия, ключевые органеллы в производстве клеточной энергии, играет важную роль в этой дисфункции тканей. В многочисленных исследованиях подчеркивается тесная связь между ожирением и дисфункцией митохондриалов адипоцита, что приводит к чрезмерному производству ROS и воспалению

The Polyphenols α-Mangostin and Nordihydroguaiaretic Acid Induce Oxidative Stress, Cell Cycle Arrest, and Apoptosis in a Cellular Model of Medulloblastoma.

Medulloblastoma is a common malignant brain tumor in the pediatric age. The current therapeutics present serious collateral effects. Polyphenols α-mangostin and nordihydroguaiaretic acid (NDGA) exert potent antitumoral activity in different cancer models, although their antitumoral effects have not been described in medulloblastoma cells yet. This study aimed to examine the proapoptotic effects of these polyphenols on human medulloblastoma cells. Medulloblastoma cell line Daoy was incubated with increasing concentrations of α-mangostin or NDGA for 24 h. The cell viability was analyzed using cr

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… Alpha mangostin induces changes in glutathione levels associated with glutathione peroxidase activity in rat brain synaptosomes. Nutr. Neurosci. 2012;15:13–19. doi: 10.1179/147683012X13327575416400. 51. Levine R.L., Williams J.A., Stadtman E.R., Shacter E. …

LncRNA Gas5, a Target of the Nonsense-Mediated Decay Pathway in the Brain, Regulates Neuroinflammation and Neurodegenerative Disease Pathways in a Tauopathy Mouse Model.

Dysregulation of target genes of nonsense-mediated decay (NMD) in the brain remains sparsely known in tauopathies. PS19 transgenic mice expressing human mutant P301S tau were evaluated for levels of lncRNA Gas5, a target of NMD. The results show Gas5 decreased in the brains of PS19 mice as they aged. We evaluated the consequences of blocking the NMD-mediated turnover of Gas5 using a small molecule administered intranasally to PS19 mice. The results show NPC86 disassociated Upf1 and Gas5, thereby hindering NMD. NPC86 treatment increased Gas5 levels in the cortex of male PS19 mice concurrent wit

Иммунитет в нейромодуляции: исследование нейронных и иммунных путей в расстройствах мозга.

Иммунитет четко регулирует функцию мозга. Она непосредственно участвует в патологических процессах таких нейродегенеративных заболеваний, как болезнь Паркинсона и Альцгеймера, посттравматические заболевания, множественный склероз, травма головного мозга и психические расстройства (большое расстройство организма, серьезное депрессивное расстройство (МДС), расстройства тревожности, расстройства психоза и шизофрения, а также расстройства нервного развития (НРД). Нейромодулирование в настоящее время является одной из ведущих терапевтических стратегий лечения этих расстройств, однако пока мало что

Xanthohumol: Mechanistic Actions and Emerging Evidence as a Multi-Target Natural Nutraceutical.

BACKGROUND: Xanthohumol (XN), a prenylated chalcone flavonoid derived from hops (Humulus lupulus), is increasingly recognized as a highly pleiotropic natural compound. OBJECTIVE: We aimed to structure XN's mechanistic hierarchy with emerging translational relevance across disease areas. METHODS: We performed a comprehensive and integrative literature review of XN for its biological and translational effects across cancer, metabolic, neurological, cardiovascular, hepatic, renal, and dermatological disorders. RESULTS: Mechanistically, XN exerts diverse bioactivities by inhibiting major pro-on

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… In synaptosomes, it inhibits 4-aminopyridine-evoked glutamate release by reducing Ca 2+ influx through N- and P/Q-type channels and suppressing Ca 2+ /calmodulin-PKA signaling via GABAa receptor engagement [ 80 ]. … Bcl-2; ↓ Apaf-1, caspase-3 | Seizure protection | Seizure severity | [ 66 ] Tau/kinase regulation | ↓ tau pS404/396/262 via PP2A & GSK3β | AD pathology ↓ | N/A | [ 64 ] Synaptic glutamate release | Presynaptic GABA_A-dependent ↓ Ca 2+ influx → CaM/PKA ↓ → glutamate release ↓ | Anti-excitotoxic | N/A (synaptosomes …

Invited Lectures : Overviews Purinergic signalling: past, present and future.

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Safety and efficacy of antigen-specific therapeutic approaches for multiple sclerosis: Systematic review.

INTRODUCTION: The objective of this systematic review is to evaluate the efficacy and safety of antigen-specific tolerance-inducing therapeutic approaches (products based on peptides, DNA and T cells) versus placebo or other comparators, where possible, in adult multiple sclerosis (MS) patients. METHODS: PubMed, CINAHL, Web of Science, Cochrane and International Clinical Trials Registry Platform, ClinicalTrials.gov were searched for published and unpublished studies. Screening, critical appraisal, and data extraction for included studies were carried out by two independent reviewers. For effi

Clinical outcomes of chemotherapy in cancer patients with different ethnicities.

BackgroundChoosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.Recent findingsPharmacogenomics, the study of how an individual's g

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… Effect of glucocorticoids on 3‐nitropropionic acid‐induced oxidative stress in synaptosomes. Eur J Pharmacol. 2004;488(1):19‐25. 84. Marsh S, McLeod HL. Thymidylate synthase pharmacogenetics in colorectal cancer. Clin Colorectal Cancer. 2001;1(3):175‐178. 85. Du X, Lai YY, Xiao Z, et al. …

Посттрансляционные изменения в нейроиммунных клетках во время нейроинфламмации: комплексные сети регулирования и терапевтические возможности.

Нейроинфламмация представляет собой общий патологический механизм, лежащий в основе широкого спектра нарушений центральной нервной системы (КНС), включая нейродегенеративные расстройства (НДД), ишемический инсульт (ИС), травматическое повреждение мозга (ТБИ) и демиелионирующие заболевания, такие как множественный склероз (МС). Этот процесс начинается с организованной реакции микроглий, астроцитов, олигодендроцитов, нейронов, эндотелиальных клеток головного мозга и проникновения в периферийные иммунные клетки. Нейроинфламмация может облегчить ремонт тканей или, наоборот, увековечить хроническое

Mechanisms of spinal glial activation in chemotherapy-induced peripheral neuropathy: Focus on microglia and astrocytes.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication in patients with malignant tumors during chemotherapy. The pathological mechanisms of CIPN remain unclear, and effective preventive and therapeutic strategies are still lacking, posing a major challenge in clinical practice. Aberrant activation of spinal glial cells, particularly microglia and astrocytes, is a key pathological hallmark of CIPN. Evidence from multiple animal models supports a causal link between glial activation and CIPN, suggesting that glial cells may serve as potential therapeutic targets. However, ow

Melatonin: Facts, Extrapolations and Clinical Trials.

Melatonin is a fascinating molecule that has captured the imagination of many scientists since its discovery in 1958. In recent times, the focus has changed from investigating its natural role as a transducer of biological time for physiological systems to hypothesized roles in virtually all clinical conditions. This goes along with the appearance of extensive literature claiming the (generally) positive benefits of high doses of melatonin in animal models and various clinical situations that would not be receptor-mediated. Based on the assumption that melatonin is safe, high doses have been a