Lipocalin 2 receptors: facts, fictions, and myths

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

Published: Aug. 11, 2023

The human 25-kDa Lipocalin 2 (LCN2) was first identified and purified as a protein that in part is associated with gelatinase from neutrophils. This shows high degree of sequence similarity the deduced sequences rat α2-microglobulin-related mouse 24p3. Based on its typical lipocalin fold, which consists an eight-stranded, anti-parallel, symmetrical β-barrel fold structure it initially thought LCN2 circulating functioning transporter small lipophilic molecules. However, studies Lcn2 null mice have shown has bacteriostatic properties plays key role innate immunity by sequestering bacterial iron siderophores. Numerous reports further involved control cell differentiation, energy expenditure, death, chemotaxis, migration, many other biological processes. In addition, important roles for health disease been multiple molecular pathways required regulation expression identified. Nevertheless, although six putative receptors proposed, there fundamental lack understanding how these cell-surface transmit amplify to cell. present review we summarize current knowledge discuss inconsistencies, misinterpretations false assumptions potential receptors.

Language: Английский

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Microglia in Ischemic Stroke: Pathogenesis Insights and Therapeutic Challenges

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 3335 - 3352

Published: May 1, 2024

Abstract: Ischemic stroke is the most common type of stroke, which main cause death and disability on a global scale. As primary immune cells in brain that are crucial for preserving homeostasis central nervous system microenvironment, microglia have been found to exhibit dual or even multiple effects at different stages ischemic stroke. The anti-inflammatory polarization release neurotrophic factors may provide benefits by promoting neurological recovery lesion early phase after However, pro-inflammatory secretion inflammatory later injury exacerbate lesion, suggesting therapeutic potential modulating balance microglial predispose them transformation Microglia-mediated signaling crosstalk with other also be key improving functional outcomes following Thus, this review provides an overview functions responses under physiological conditions, including activation, polarization, interactions cells. We focus approaches promote microglia, inhibit enhance beneficial cell-to-cell interactions. These targets hold promise creation innovative strategies. Keywords: phagocytosis, crosstalk, anti-inflammatory,

Language: Английский

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Advancing stroke therapy: innovative approaches with stem cell-derived extracellular vesicles

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 22, 2024

Abstract Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window associated risks underscore necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as promising therapeutic approach due to ability modulate post-stroke microenvironment facilitate neuroprotection neurorestoration. This review synthesizes current research on potential stem EVs AIS, focusing origin, biogenesis, mechanisms action, strategies enhancing targeting capacity efficacy. Additionally, we explore innovative combination therapies discuss both challenges prospects EV-based treatments. Our findings reveal that exhibit diverse effects such promoting neuronal survival, diminishing neuroinflammation, protecting blood-brain barrier, angiogenesis neurogenesis. Various strategies, including modifications cargo modifications, been developed improve efficacy EVs. Combining other treatments, therapy, cell transplantation, nanomedicine, gut microbiome modulation, holds great promise improving outcomes. However, heterogeneity need standardized protocols EV production quality control remain be addressed. represent avenue offering address limitations Further needed optimize translate benefits clinical practice, an emphasis ensuring safety, overcoming regulatory hurdles, specificity delivery target tissues. Graphical

Language: Английский

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Lipocalin-2 aggravates blood-brain barrier dysfunction after intravenous thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway

Redox Biology, Journal Year: 2024, Volume and Issue: 76, P. 103342 - 103342

Published: Sept. 6, 2024

Disruption of the blood-brain barrier (BBB) is a major contributor to hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis (IVT). However, clinical therapies aimed at BBB protection after IVT remain limited.

Language: Английский

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LCN2 induces neuronal loss and facilitates sepsis-associated cognitive impairments

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 1, 2025

Abstract Sepsis-associated encephalopathy (SAE) is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis. Despite increasing data supporting the hypothesis of neuronal damage, exact mechanism sepsis-related cognitive disorders and therapeutic strategies remain unclear need further investigation. In this study, sepsis model was established in C57 mice using lipopolysaccharide (LPS). The findings demonstrated that LPS exposure induced loss, synaptic deficits accompanied mitochondrial damage. Bioinformatics western blot analyses significant increase Lipocalin-2 (LCN2) during as key hub gene involved immune inflammation. Interestingly, recombinant LCN2 protein exhibited similar effects on dysfunction mice. Conversely, downregulating effectively nullified impact LPS, leading amelioration deficits, reactive oxygen species (ROS)-associated These suggest novel etiopathogenic SAE, which initiated increased LCN2, loss deficit. Inhibition could be therapeutically beneficial treating sepsis-induced impairments.

Language: Английский

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Mechanism of LCN2 in cerebral ischemia-reperfusion injury

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

Published: March 20, 2025

Cerebral ischemia-reperfusion injury (CIRI) is a complex pathophysiological process faced by brain tissues after ischemic stroke treatment, which involves mechanisms of inflammatory response, oxidative stress and apoptosis, severely affects treatment outcome. Lipocalin-2 (LCN2), an acute-phase protein, significantly up-regulated CIRI promotes neural repair enhancing astrocyte phagocytosis, but its over-activation may also trigger secondary inflammation demyelination injury. LCN2 plays key role in neuroinflammation regulation regulating the polarization state astrocytes release factors, affect integrity blood–brain barrier variety pathologic processes. In view important CIRI, this article reviews mechanism LCN2, aiming to provide new ideas methods for stroke.

Language: Английский

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Astrocyte heterogeneity in ischemic stroke: Molecular mechanisms and therapeutic targets

Neurobiology of Disease, Journal Year: 2025, Volume and Issue: unknown, P. 106885 - 106885

Published: March 1, 2025

Language: Английский

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Hydroxysafflower yellow A alleviates the inflammatory response in astrocytes following cerebral ischemia by inhibiting the LCN2/STAT3 feedback loop

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(4)

Published: March 26, 2025

Language: Английский

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Endurance Exercise Training Alleviates Hepatic Lipocalin‐2 Release and Prevents Anxiety‐Like Disorders in Chronically Stressed Mice

Advanced Biology, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Abstract Exercise training can prevent anxiety disorders in both rodent models and human cohorts. The involvement of peripheral factors exercise‐mediated mental health is being appreciated. It recently shown that the hepatic biosynthesis lipocalin‐2 (LCN2) respond to chronic restraint stress (CRS) elicit anxiety‐like behaviors via inhibiting neural activity medial prefrontal cortex (mPFC). Here, it found 14‐day treadmill exercise ameliorates these CRS‐treated mice. Further assays show intervention reduces release LCN2. Meanwhile, may also counteract adverse effect LCN2 relieving cortical microglial cell proliferation. results collectively suggest modulate liver‐brain axis reshape for preventing disorders.

Language: Английский

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Optimizing lipocalin sequence classification with ensemble deep learning models

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(4), P. e0319329 - e0319329

Published: April 16, 2025

Deep learning (DL) has become a powerful tool for the recognition and classification of biological sequences. However, conventional single-architecture models often struggle with suboptimal predictive performance high computational costs. To address these challenges, we present EnsembleDL-Lipo, an innovative ensemble deep framework that combines Convolutional Neural Networks (CNNs) (DNNs) to enhance identification lipocalin Lipocalins are multifunctional extracellular proteins involved in various diseases stress responses, their low sequence similarity occurrence ‘twilight zone’ alignment significant hurdles accurate classification. These challenges necessitate efficient methods complement traditional, labor-intensive experimental approaches. EnsembleDL-Lipo overcomes issues by leveraging set PSSM-based features train large models. The integrates multiple feature representations derived from position-specific scoring matrices (PSSMs), optimizing across diverse patterns. model achieved superior results on training dataset, accuracy (ACC) 97.65%, recall 97.10%, Matthews correlation coefficient (MCC) 0.95, area under curve (AUC) 0.99. Validation independent test further confirmed robustness model, yielding ACC 95.79%, 90.48%, MCC 0.92, AUC 0.97. demonstrate is highly effective computationally identification, significantly outperforming existing offering strong potential applications biomarker discovery.

Language: Английский

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