Advances in the Regulation of Inflammatory Mediators in Nitric Oxide Synthase: Implications for Disease Modulation and Therapeutic Approaches

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1204 - 1204

Published: Jan. 30, 2025

Nitric oxide synthases (NOS) are crucial enzymes responsible for the production of nitric (NO), a signaling molecule with essential roles in vascular regulation, immune defense, and neurotransmission. The three NOS isoforms, endothelial (eNOS), neuronal (nNOS), inducible (iNOS), tightly regulated by inflammatory mediators cellular pathways. While physiological NO is vital maintaining homeostasis, dysregulated activity contributes to pathogenesis numerous diseases, including cardiovascular disorders, neurodegenerative conditions, cancer. Recent advances understanding molecular mechanisms regulation have unveiled novel therapeutic opportunities, isoform-specific modulators, upstream pathways, nanotechnology-enhanced delivery systems. This review highlights these advancements, offering insights into how targeting its regulatory network can enable precise effective strategies managing inflammation-driven pathologies.

Language: Английский

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Alzheimer's disease neuropathology and its estimation with fluid and imaging biomarkers

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 14, 2025

Abstract Alzheimer’s disease (AD) is neuropathologically characterized by the extracellular deposition of amyloid-β peptide (Aβ) and intraneuronal accumulation abnormal phosphorylated tau (τ)-protein (p-τ). Most frequently, these hallmark lesions are accompanied other co-pathologies in brain that may contribute to cognitive impairment, such as vascular lesions, transactive-response DNA-binding protein 43 (TDP-43), and/or α-synuclein (αSyn) aggregates. To estimate extent AD patients, several biomarkers have been developed. Specific tracers target visualize Aβ plaques, p-τ αSyn pathology or inflammation positron emission tomography. In addition imaging biomarkers, cerebrospinal fluid, blood-based biomarker assays reflecting AD-specific non-specific processes either already clinical use development. this review, we will introduce pathological brain, related discuss what respective determined at post-mortem histopathological analysis. It became evident initial stages plaque not detected with currently available biomarkers. Interestingly, precedes deposition, especially beginning when unable detect it. Later, takes lead accelerates pathology, fitting well known evolution measures over time. Some still lack clinically established today, TDP-43 cortical microinfarcts. summary, specific for AD-related pathologies allow accurate diagnosis based on pathobiological parameters. Although current excellent pathologies, they fail which analysis required. Accordingly, neuropathological studies remain essential understand development early stages. Moreover, there an urgent need co-pathologies, limbic predominant, age-related encephalopathy-related modify interacting p-τ. Novel approaches vesicle-based cryptic RNA/peptides help better future.

Language: Английский

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Immune modulation to treat Alzheimer’s disease

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 31, 2025

Abstract Immune mechanisms play a fundamental role in Alzheimer’s disease (AD) pathogenesis, suggesting that approaches which target immune cells and immunologically relevant molecules can offer therapeutic opportunities beyond the recently approved amyloid beta monoclonal therapies. In this review, we provide an overview of immunomodulatory therapeutics development, including their preclinical evidence clinical trial results. Along with detailing processes involved AD pathogenesis highlighting how these be therapeutically targeted to modify progression, summarize knowledge gained from previous trials immune-based interventions, series recommendations for development future treat AD.

Language: Английский

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Knowing the enemy: strategic targeting of complement to treat Alzheimer disease

Nature Reviews Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Language: Английский

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Amyloid immunotherapy for Alzheimer's disease: the case for cautious adoption

Arquivos de Neuro-Psiquiatria, Journal Year: 2025, Volume and Issue: 83(05), P. 001 - 004

Published: May 1, 2025

Abstract The licensing of lecanemab and donanemab, disease-modifying immunotherapies for Alzheimer's disease (AD) targeting β-amyloid pathology, has been met with difference in opinion about efficacy, adverse effects, cost-effectiveness. Here we summarize the current situation make case cautious adoption these treatments into clinical practice. This is predicated on four main observations: 1) impact core pathologies AD result meaningful benefits; 2) while effects can be serious, are proving manageable practice; 3) upscaling services to deliver agents likely provide wider benefits diagnosing treating dementia facilitating future from drug pipeline; 4) factoring both societal cost care potential continued accrual long term will bring within acceptable cost-effectiveness thresholds.

Language: Английский

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Zooming in on brain inflammation in Alzheimer’s disease

Brain, Journal Year: 2025, Volume and Issue: 148(1), P. 1 - 2

Published: Jan. 1, 2025

Language: Английский

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Neuroprotective potential of tranilast in streptozotocin-induced sporadic Alzheimer's disease model targeting TXNIP-NLRP3 inflammasome pathway

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 156, P. 114691 - 114691

Published: April 23, 2025

Language: Английский

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Developing Non-Invasive Molecular Markers for Early Risk Assessment of Alzheimer's Disease

Biomarkers in Neuropsychiatry, Journal Year: 2025, Volume and Issue: unknown, P. 100120 - 100120

Published: Jan. 1, 2025

Language: Английский

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Editorial: Function and regulation of non-neuronal cells in the nervous system

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 7, 2025

Traditionally, the nervous system has been perceived primarily as a complex network predominantly composed of neurons. Nevertheless, ongoing developments in field neuroscience have brought to light significant contributions non-neuronal cells, highlighting their importance 1,2 . Getting profound insight into functional traits and mechanisms that govern them is essential for developing innovative approaches treating preventing neurological disorders.Recently, there progress investigation cells within system. The primary emphasis lies uncovering intricate interactions connect these neurons each other. As an illustration, recent studies neurovascular coupling begun elucidate relationship between brain activity modulation blood flow cerebral [3][4][5][6] Investigations neuroimmunology introduced novel insights critical roles immune play both inflammatory response progression neurodegenerative disorders 7,8 Investigating glial serves burgeoning area study, focusing on unraveling complexities communication exchange information among astrocytes, other neurons, along with influence neural operations 2,9,10 .Microglia, resident found system, act initial barrier against invasive pathogens role upholding balance environment 11 These part processes such elimination excess synapses throughout maturation are capable rapidly triggering protective when faced injury or pathological conditions [12][13][14] Astrocytes vital not only offering structural support but also expertly managing neurotransmitter absorption release 15,16 , meticulously maintaining ion equilibrium 17,18 influencing synaptic adaptability 19 Cells unit, including endothelial pericyte populations, stability integrity blood-brain while ensuring accurate suitable regulation perfusion 20,21 .In disorders, unnormal functioning commonly identified. In Alzheimer's Parkinson's diseases, involvement astrocytes become characteristic feature [22][23][24] Additionally, impairments link function vascular responses disruptions factors development numerous stroke multiple sclerosis [25][26][27] Consequently, thorough exploration functions disease anticipated yield perspectives strategic avenues identifying new therapeutic targets.This special issue provides examination important aspects regarding Non-neuronal (mainly cells) supporting, protecting, nourishing Their ability divide makes prone mutation malignant transformation. Most tumors central originate from cells. Ji et al reported discovery Gap Junction Protein, Gamma 1(GJC1) prognostic biomarker glioma 28 GJC1 located human chromosome 17 encodes gap junction gamma -1 protein (connexin 45, Cx45), which participates intercellular communication. expression Cx45 decreased colorectal cancer tumor-suppressive melanoma its gliomas remains unclear. study systematically investigated clinicopathological features, molecular subclasses, prognosis patterns. They analyzed biological markers associated tumor further performed drug correlation analysis. Moreover, all specific action obtained analysis were related cell cycle, supporting cell-cycle regulation.The review article Zhao comprehensively stated olfactory system's complexity pivotal health 29 This discussed diverse dynamics mammalian bulb, mainly focused microglia, oligodendrocytes, ensheathing radial glia Each type contributes uniquely bulb 's functionality, many neuronal survival defense axonal guidance. features health, potential applications neuroregeneration.Traumatic (TBI) global concern characterized by elevated rates morbidity mortality. physiological changes after TBI closely microglia. Microglia, brain, linked treatment TBI. Zhang published bibliometric visualization identify current research hotspots predict future 30 this authors mechanism ischemic two aspects: repair infiltration following post-TBI peripheral immunosuppression inflammation.Ischemic accounts 75% 80% events, making it leading cause cerebrovascular diseases deaths worldwide 31 Following stroke, crucial unit functions, regulating metabolic Wang al. systemically explored trends prospects immune-related therapy 32 .To summarize, currently experiencing growth. dedicated Research Topic intended significantly advancement establishing platform academic discussions demonstration achievements.

Language: Английский

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Mapping of catecholaminergic denervation, neurodegeneration, and inflammation in 6-OHDA-treated Parkinson’s disease mice

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 11, 2025

Efforts to develop disease-modifying treatments for Parkinson's disease (PD) have been hindered by the lack of animal models replicating all hallmarks PD and insufficient attention extra-nigrostriatal regions pathologically critical prodromal appearance non-motor symptoms. Among models, 6-hydroxydopamine (6-OHDA) infusion in mice has gained prominence since 2012, primarily focusing on nigrostriatal region. This study characterized tyrosine hydroxylase-positive neuron fiber loss across brain following a unilateral 6-OHDA (20 µg) into dorsal striatum. Our analysis integrates immunolabeling, clearing (iDISCO+), light sheet microscopy, computational methods, including fMRI machine learning tools. We also examined sex differences, progression, neuroinflammatory responses, pro-apoptotic signaling C57BL/6 exposed varying dosages (5, 10, or 20 followed 1, 7, 14 days recovery. comprehensive, spatiotemporal 6-OHDA-induced pathology was used map time course neuronal degeneration onset neuroinflammation.

Language: Английский

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