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Xanthoceras sorbifolia extracts ameliorate dendritic spine deficiency and cognitive decline via upregulation of BDNF expression in a rat model of Alzheimer's disease.

Xanthoceras sorbifolia, a traditional Chinese folk medicine with anti-inflammatory effects, has been used for a long time in China, especially in the Inner Mongolian area for the treatment of rheumatism. Inflammation is one of the main causes of Alzheimer's disease (AD). AD is characterized by aggregation of amyloid β-peptide (Aβ) plaques, neurofibrillary tangle formation, synaptic dysfunction and neuronal loss. To investigate whether Xanthoceras sorbifolia extracts (XSE) improve cognition and protect dendritic spines, we performed behavioral tests to investigate learning and memory in an Aβ25

Induction of DARPP-32 by brain-derived neurotrophic factor in striatal neurons in vitro is modified by histone deacetylase inhibitors and Nab2.

Neurotrophins and modifiers of chromatin acetylation and deacetylation participate in regulation of transcription during neuronal maturation and maintenance. The striatal medium spiny neuron is supported by cortically-derived brain derived neurotrophic factor and is the most vulnerable neuron in Huntington's disease, in which growth factor and histone deacetylase activity are both disrupted. We examined the ability of three histone deacetylase inhibitors, trichostatin A, valproic acid and Compound 4 b, alone and combined with brain derived neurotrophic factor (BDNF), to promote phenotypic matu

CYP46A1 gene therapy deciphers the role of brain cholesterol metabolism in Huntington's disease.

Dysfunctions in brain cholesterol homeostasis have been extensively related to brain disorders. The main pathway for brain cholesterol elimination is its hydroxylation into 24S-hydroxycholesterol by the cholesterol 24-hydrolase, CYP46A1. Increasing evidence suggests that CYP46A1 has a role in the pathogenesis and progression of neurodegenerative disorders, and that increasing its levels in the brain is neuroprotective. However, the mechanisms underlying this neuroprotection remain to be fully understood. Huntington's disease is a fatal autosomal dominant neurodegenerative disease caused by an

Brain-derived neurotrophic factor acutely depresses excitatory synaptic transmission to GABAergic neurons in visual cortical slices.

Brain-derived neurotrophic factor (BDNF) acutely modulates synaptic transmission to excitatory neurons in hippocampus and neocortex. The question of whether BDNF acts similarly on excitatory synaptic transmission to GABAergic neurons was eluded in previous studies using cortical slices. To address this question, we used transgenic mice in which expression of green fluorescence protein (GFP) is regulated by glutamic acid decarboxylase 67 (GAD67) promoter. In cortical slices prepared from these GAD67-GFP knock-in mice, we could detect GABAergic neurons under a fluorescent microscope. An applicat

Oncogenic influences of neurotrophin receptors: Shedding light on Trk biology.

During critical stages of neurodevelopment, tropomyosin receptor kinase receptors, encoded by NTRK genes, exhibit temporally driven differential peaks of expression to properly guide the establishment of the peripheral and central nervous systems. In addition, these neuronal systems exhibit non-canonical regulation of surrounding tissues, impacting organogenesis, homeostasis, plasticity, and regeneration. The same processes that guide neurodevelopment, such as differentiation, plasticity, and neuronal survival, are also hijacked in cancer, making the NTRK family an ideal candidate to study. Th

New Insights into the Pathogenesis of Systemic Mastocytosis.

Mastocytosis is a type of myeloid neoplasm characterized by the clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells that infiltrate one or more organ systems. Systemic mastocytosis (SM) is a more aggressive variant of mastocytosis with extracutaneous involvement, which might be associated with multi-organ dysfunction or failure and shortened survival. Over 80% of patients with SM carry the KIT D816V mutation. However, the KIT D816V mutation serves as a weak oncogene and appears to be a late event in the pathogenesis of mastocytosis. The management o

MGluR5 Agonist, CHPG, увеличивает число дифференцированных человеческих олигодендроцитов.

Предыдущие исследования на взрослых мышах показывают, что 2-хлор-5-гидроксифениловый гликин (CHPG) MGluR5 сокращает потери в миелине, вызванные купризоной. Этот эффект частично привязывается CHPG к рецепторам mGluR5 для реактивных астроцитов, что приводит к высвобождению нервно-партрофного фактора мозга (BDNF), что приводит к увеличению миелина и уменьшает поведенческий дефицит. Однако остается неясным, оказывает ли CHPG аналогичное благотворное воздействие на клетки человека. Для решения этой проблемы мы изучили воздействие CHPG на клетки человека, используя как индуцированные плюрипотентными

The influence of neuro-tumor interactions on tumorigenesis and therapeutic response.

The intricate crosstalk between the nervous system and tumors has emerged as a pivotal determinant of tumorigenesis, progression, and therapeutic response. This review synthesizes current insights into neuro-tumor interactions, highlighting how neuronal networks within the tumor microenvironment (TME) modulate cancer cell proliferation, invasion, and angiogenesis by releasing neurotransmitters, growth factors, etc. The neuro-immune axis, a critical interface linking neural signaling to immune regulation, is explored in depth, elucidating how neuronal-derived molecules influence the phenotype a

Dysregulated TRK signalling is a therapeutic target in CYLD defective tumours.

Individuals with germline mutations in the tumour-suppressor gene CYLD are at high risk of developing disfiguring cutaneous appendageal tumours, the defining tumour being the highly organised cylindroma. Here, we analysed CYLD mutant tumour genomes by array comparative genomic hybridisation and gene expression microarray analysis. CYLD mutant tumours were characterised by an absence of copy-number aberrations apart from LOH chromosome 16q, the genomic location of the CYLD gene. Gene expression profiling of CYLD mutant tumours showed dysregulated tropomyosin kinase (TRK) signalling, with overex

Фитохимические вещества, направляемые на сигнализацию BDNF для лечения неврологических расстройств.

Неврологические расстройства определяются ухудшением или нарушением структуры и функции нервной системы. Эти заболевания, включая множественный склероз, болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и шизофрению, вызваны сложными патологическими процессами, в том числе эксцитотоксичностью, нейроинфламмацией, окислительным стрессом, генетическими мутациями и скомпрометированным нейротрофическим сигналом. Несмотря на то, что в настоящее время лекарственные препараты устраняют симптомы, их долгосрочная эффективность ограничена из-за неблагоприятных побочных эффектов и слабых нейроз

Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain.

The neurotransmitter GABA is normally characterized as having an inhibitory effect on neural activity in the adult central nervous system (CNS), which quells over-excitation and limits neural plasticity. Spinal cord injury (SCI) can bring about a modification that weakens the inhibitory effect of GABA in the central gray caudal to injury. This change is linked to the downregulation of the potassium/chloride cotransporter (KCC2) and the consequent rise in intracellular Cl- in the postsynaptic neuron. As the intracellular concentration increases, the inward flow of Cl- through an ionotropic GABA

Трекеты (Trk-Targeting Drugs): Новинная терапия различных заболеваний.

Многие маршруты могут привести к переходу от здорового к больному фенотипу. Однако не так уж много путей, чтобы двигаться в противоположном направлении, т.е. Таким образом, остается следующий насущный вопрос: каковы патогенные пути и как можно противодействовать им в терапевтических целях? Человеческие клетки содержат >500 белковые киназы и почти 200 белковые фосфаты, действующие на тысячи белков, включая факторы роста клеток. Здесь мы обсуждаем нейтрофины с патогенными или метаботрофными способностями, в частности нейротрофический фактор, полученный из мозга, фактор нервного роста (НГФ), про-

Раскрывая причинно-следственную связь между ожирением и множественным склерозом: систематический обзор литературы.

Множественный склероз (MS) представляет собой многогранное нейродегенеративное расстройство под влиянием генетики и образа жизни. В рамках этого систематического обзора литературы изучается роль six Гены, связанные с ожирением, включая жировую массу и ожирение (FTO), ингибиторную молекулу FAS 2 (FAIM2), тип болезни Ньеманн-пиков C1-like 1 (НПК-1), glucosamine-6-phosphate daminase 2 (ВНПДА2), melanocortin-4 Рецептор (MC4R) и нейротрофический коэффициент, полученный из мозга (BDNF) в контексте MS. МЕТОДЫ: Поиск литературы осуществлялся с использованием баз данных Embase, Scopus, Cochrane, Web of

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… Its receptor, TrkB, is upregulated near MS plaques, suggesting a role in neuronal protection and myelin integrity (Hohlfeld 2008 ; Nociti and Romozzi 2023 ). …

Cancer Neoaxonogenesis: Mechanisms and Factors Involved in the Recruitment of Peripheral Nerves by Cancer Tissue.

Peripheral nerves provide a direct connection between the brain and the tumor microenvironment. This connection allows the nervous system to influence processes associated with the development, progression, and metastasis of different tumor types. Therefore, tumor innervation by peripheral nerve fibers is currently emerging as a characteristic that contributes to multiple hallmarks of cancer. Several experimental studies have shown that cancer progression involves actively inducing the ingrowth of autonomic and sensory nerve fibers into tumor tissue. In this process, known as neoaxonogenesis,

Myokines in cancer: bridging molecular mechanisms to biomarker discovery and therapeutic innovation.

Exercise can regulate the physiological functions of the body by inducing the secretion of myokines, which are bioactive factors mainly secreted by muscle cells. This review classifies myokines based on their functional characteristics, including metabolic regulation (such as myostatin, interleukin-6), neuroregulation (brain-derived neurotrophic factor), cell proliferation/differentiation regulation (myogenic proteins), immune regulation (tumor necrosis factor- alpha), and factors involved in angiogenesis and extracellular matrix remodeling (such as connective tissue growth factor).Cancer, as

Emerging mechanism and therapeutic potential of neurofibromatosis type 1-related nerve system tumor: Advancing insights into tumor development.

Neurofibromatosis Type 1 (NF1) is a genetic disorder resulting from mutations in the NF1 gene, which increases susceptibility to various nervous system tumors, including plexiform neurofibromas, malignant peripheral nerve sheath tumors, and optic pathway gliomas. Recent research has shown that these tumors are intricately connected to the complex, dynamic interactions within neurons, culminating in neuronal signaling that fosters tumor growth. These interactions offer crucial insights into the molecular mechanisms underpinning tumor development, as well as broader implications for therapeutic

Association of the Val66Met Polymorphism of the BDNF Gene with the Depression in a Mexican Population with Multiple Sclerosis.

UNLABELLED: Multiple sclerosis (MS) is a chronic, autoimmune pathology that affects the nervous system. It is characterized by inflammatory lesions that cause axonal damage with neurodegeneration. The signs and symptoms present in this pathology include among others, psychiatric disorders. In MS, depression is the most frequent psychiatric disorder, with prevalence levels of 40 to 60%; to date, the cause is unknown. The brain-derived neurotrophic factor (BDNF) is a neurotrophin related to neuroplasticity. The single-nucleotide polymorphism Val66Met, encoded by the BDNF gene, has been associate

NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance.

Neurotrophic tropomyosin receptor kinase (NTRK) gene fusion has been identified as an oncogenic driver of various solid tumors, and it is rare in non-smalll cell lung cancer (NSCLC) with a frequency of approximately less than 1%. Next-generation sequencing (NGS) is of priority for detecting NTRK fusions, especially RNA-based NGS. Currently, the tropomyosin receptor kinase (TRK) inhibitors have shown promising efficacy and well tolerance in patients with NTRK fusion-positive solid tumors, regardless of tumor histology. The first-generation TRK inhibitors (larotrectinib and entrectinib) are reco

Сравнительный анализ нервно-воспалительных путей болезни Альцгеймера, болезни Паркинсона и множественного склероза: понимание сходства и различий.

Растет интерес к нейродегенеративным болезням, усугубляющим значительное социально-экономическое бремя, вызванное старением общества. Несмотря на то, что каждая болезнь имеет различные этиологии, нейроинфламмация, как считается, играет решающую роль в болезни Альцгеймера (AD), болезни Паркинсона (PD) и множественном склерозе (MS). Помимо патогенной функции воспаления мозга, растет число свидетельств того, что иммунная реакция необходима для нейрорегенерации. Этот обзор сравнивает и контрастирует с нейроинфламационными путями, которые характерны для различных нейродегенеративных заболеваний. В

Review of the Agnostic-Type Treatment Approach: Treating Cancer by Mutations, Not by Location.

Recent years has seen the discovery and description of genetic alterations responsible for oncogenesis in a wide variety of cancers, together with the finding that some markers are actionable and can be targeted by medications. Such developments have enabled cancer treatments to evolve from empirical palliative chemotherapy, with low chances of response or curative intent in most types of cancers, to targeted therapy, with some studies showing promising results in terms of improved overall response rates, overall survival and quality of life, although, like all new groups of medications, with