Neutrophil extracellular traps in homeostasis and disease

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 20, 2024

Language: Английский

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Significance of Programmed Cell Death Pathways in Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9947 - 9947

Published: Sept. 15, 2024

Programmed cell death (PCD) is a form of distinct from accidental (ACD) and also referred to as regulated (RCD). Typically, PCD signaling events are precisely by various biomolecules in both spatial temporal contexts promote neuronal development, establish neural architecture, shape the central nervous system (CNS), although role extends beyond CNS. Abnormalities cascades contribute irreversible loss cells function, leading onset progression neurodegenerative diseases. In this review, we summarize molecular processes features different modalities PCD, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, other novel forms their effects on pathogenesis diseases, such Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), multiple (MS), traumatic brain injury (TBI), stroke. Additionally, examine key factors involved these pathways discuss potential for development therapeutic targets strategies. Therefore, strategies targeting inhibition or facilitation offer promising approach clinical applications treating

Language: Английский

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Diabetes-associated neutrophil NETosis: pathogenesis and interventional target of diabetic complications

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 3, 2023

Neutrophil extracellular traps (NETs) are known as fibers networks consisting of antimicrobial proteins and decondensated chromatin DNA released by activated neutrophils. NETosis is a NETs-induced neutrophilic cell death which unique from necrosis or apoptosis. Besides its neutralizing pathogen, plays crucial role in diabetes diabetes-related complications. In patients with diabetes, NETs-releasing products significantly elevated blood, these findings confirm the association diabetic complications, including wound healing, retinopathy, atherosclerosis. This article briefly summarizes mechanisms discusses contribution to pathogenesis complications suggests new therapeutic targets some small molecule compounds.

Language: Английский

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Role of Mitochondria in the Regulation of Effector Functions of Granulocytes

Cells, Journal Year: 2023, Volume and Issue: 12(18), P. 2210 - 2210

Published: Sept. 5, 2023

Granulocytes (neutrophils, eosinophils, and basophils) are the most abundant circulating cells in innate immune system. Circulating granulocytes, primarily neutrophils, can cross endothelial barrier activate various effector mechanisms to combat invasive pathogens. Eosinophils basophils also play an important role allergic reactions antiparasitic defense. regulate response, wound healing, tissue repair by releasing of cytokines lipid mediators. The granulocytes include production reactive oxygen species (ROS), degranulation, phagocytosis, formation DNA-containing extracellular traps. Although all glycolytic have only a small number mitochondria, growing body evidence suggests that mitochondria involved functions as well mediators apoptosis. It has been shown mitochondrial ROS controls signaling pathways mediate activation stimuli. In this review, we will briefly discuss data on regulation other granulocytes.

Language: Английский

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Neutrophil extracellular traps in intracerebral hemorrhage: implications for pathogenesis and therapeutic targets

Metabolic Brain Disease, Journal Year: 2023, Volume and Issue: 38(8), P. 2505 - 2520

Published: July 24, 2023

Language: Английский

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Roles of Oxidative Stress and Autophagy in Alcohol-Mediated Brain Damage

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 302 - 302

Published: Feb. 28, 2025

Excessive alcohol consumption significantly impacts human health, particularly the brain, due to its susceptibility oxidative stress, which contributes neurodegenerative conditions. Alcohol metabolism in brain occurs primarily via catalase, followed by CYP2E1 pathways. Excess metabolized generates reactive oxygen/nitrogen species (ROS/RNS), leading cell injury altering many different Elevated stress impairs autophagic processes, increasing post-translational modifications and further exacerbating mitochondrial dysfunction ER death. The literature highlights that alcohol-induced disrupts autophagy mitophagy, contributing neuronal damage. Key mechanisms include dysfunction, epigenetics, accumulation of oxidatively modified proteins, lead neuroinflammation impaired cellular quality control. These processes are exacerbated chronic exposure, resulting suppression protective pathways like NRF2-mediated antioxidant responses increased changes brain. Alcohol-mediated neurotoxicity involves complex interactions between metabolism, regulation, influenced various factors such as drinking patterns, nutritional status, genetic/environmental factors, highlighting need for molecular studies unravel these develop targeted interventions.

Language: Английский

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The Crosstalk Between NETs and the Complement Cascade: An Overview in Nephrological Autoimmune Disease

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2789 - 2789

Published: March 20, 2025

The complement cascade and Neutrophil Extracellular Traps (NETs) represent fundamental tools in protecting the host from foreign pathogens. Complement components relative fragments, classically assigned to innate immunity, a key link with humoral immune response. NETs are crucial component of response, consisting chromatin release activated neutrophils. These web-like structures facilitate pathogen entrapment elimination through proteolytic degradation antimicrobial effectors. Previous findings suggested have significant role pathogenesis several diseases characterized by inflammation, such as autoimmune infectious diseases. However, crosstalk between has only recently been investigated, aspects still need be fully clarified. Recent evidence seems suggest bidirectional NETosis. We here present interaction specific that mostly affect kidney, systemic lupus erythematosus, Antineutrophilic Cytoplasmic Antibody (ANCA)-associated vasculitis antiphospholipid syndrome. mechanisms reported may targets for development possible therapeutic strategies.

Language: Английский

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Stages of NETosis Development upon Stimulation of Neutrophils with Activators of Different Types

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12355 - 12355

Published: Aug. 2, 2023

Before NETs are released, the neutrophil undergoes structural changes. First, it flattens, accompanied by a change in cell shape and rearrangement of cytoskeleton. Then, nuclear swelling begins, which ends with ejection into extracellular space. We used widefield confocal fluorescence microscopy to register morphological changes neutrophils during activation NETosis. Different types activators were used, such as NOX-dependent PMA calcium ionophore A23187. The measurements performed series sequential stages. In first stage (30 s after addition immediately stimulation neutrophils), response A23187 exposure was studied. Subsequently, characteristics different phases examined over longer period time (30, 60, 120, 180, 240 min). specific features NETosis development analyzed separately. During 30 s, appeared be heterogeneous structure actin Characteristic shapes included 30″ type 1 cells, similar control, F-actin concentrated center cytoplasm, 2 had flattened (spread) increased frontal dimensions distributed throughout cell. Later, swelling, corresponding membranes, NET release space evaluated. conditions determining initiation chromatin two characteristic decondensed revealed. results obtained contribute better understanding biophysical mechanisms development.

Language: Английский

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Morphology of Neutrophils during Their Activation and NETosis: Atomic Force Microscopy Study

Cells, Journal Year: 2023, Volume and Issue: 12(17), P. 2199 - 2199

Published: Sept. 2, 2023

Confocal microscopy and fluorescence staining of cellular structures are commonly used to study neutrophil activation NETosis. However, they do not reveal the specific characteristics membrane surface, its nanostructure, morphology. The aim this was topography nanosurface neutrophils during NETosis using atomic force (AFM). We showed main stages NETosis, which include control cell spreading, fragment formation, fusion nuclear segments, disruption, release extracellular traps (NETs), final disintegration. Changes in parameters were quantified. It shown that with increasing time there a decrease spectral intensity spatial periods. Exposure activator A23187 resulted an increase number average size fragments over time. activators PMA (phorbol 12-myristate 13-acetate) caused same pattern transformation from spherical cells segmented nuclei disrupted NET release. induced earlier than PMA, but more at end specified interval (180 min). In our study, we AFM as research tool. laser-scanning (CLSM) images provided for identification detailed analysis phenomena studied. way, exploited advantages both techniques.

Language: Английский

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Neutrophil PPIF exacerbates lung ischemia–reperfusion injury after lung transplantation by promoting calcium overload-induced neutrophil extracellular traps formation

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 142, P. 113051 - 113051

Published: Sept. 4, 2024

Language: Английский

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