7,280 results match your criteria reactive astrocytes


Shenqi Yizhi Granule attenuates Aβ induced cognitive dysfunction via inhibiting JAK2/STAT3 activated astrocyte reactivity.

Exp Gerontol 2021 May 8:111400. Epub 2021 May 8.

Institute of Meterial Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China. Electronic address:

Shenqi Yizhi Granule (SYG), a modern preparation herbs based on the theory of traditional Chinese medicine, has been proved to be effective against Alzheimer's disease in clinical trials, APP/PS1 mice and 5XFAD transgenic mice. But the underlying mechanism remains ambiguous. Increasing evidence supports the crucial role of astrocyte reactivity in the pathogenesis of Alzheimer's disease (AD). Read More

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The Pathological Role of Astrocytic MAOB in Parkinsonism Revealed by Genetic Ablation and Over-expression of MAOB.

Exp Neurobiol 2021 Apr;30(2):113-119

Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.

The cause of Parkinson's disease has been traditionally believed to be the dopaminergic neuronal death in the substantia nigra pars compacta (SNpc). This traditional view has been recently challenged by the proposal that reactive astrocytes serve as key players in the pathology of Parkinson's disease through excessive GABA release. This aberrant astrocytic GABA is synthesized by the enzymatic action of monoamine oxidase B (MAOB), whose pharmacological inhibition and gene-silencing are reported to significantly alleviate parkinsonian motor symptoms in animal models of Parkinson's disease. Read More

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IL-9-triggered lncRNA Gm13568 regulates Notch1 in astrocytes through interaction with CBP/P300: contribute to the pathogenesis of experimental autoimmune encephalomyelitis.

J Neuroinflammation 2021 May 11;18(1):108. Epub 2021 May 11.

Xuzhou Key Laboratory of Neurobiology, Department of Neurobiology and Anatomy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.

Background: Interleukin 9 (IL-9), produced mainly by T helper 9 (Th9) cells, has been recognized as an important regulator in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Astrocytes respond to IL-9 and reactive astrocytes always associate with blood-brain barrier damage, immune cell infiltration, and spinal injury in MS and EAE. Several long non-coding RNAs (lncRNAs) with aberrant expression have been identified in the pathogenesis of MS. Read More

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Recovery of Depleted miR-146a in ALS Cortical Astrocytes Reverts Cell Aberrancies and Prevents Paracrine Pathogenicity on Microglia and Motor Neurons.

Front Cell Dev Biol 2021 23;9:634355. Epub 2021 Apr 23.

Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal.

Reactive astrocytes in Amyotrophic Lateral Sclerosis (ALS) change their molecular expression pattern and release toxic factors that contribute to neurodegeneration and microglial activation. We and others identified a dysregulated inflammatory miRNA profile in ALS patients and in mice models suggesting that they represent potential targets for therapeutic intervention. Such cellular miRNAs are known to be released into the secretome and to be carried by small extracellular vesicles (sEVs), which may be harmful to recipient cells. Read More

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White matter abnormalities and iron deposition in prenatal mucolipidosis IV- fetal imaging and pathology.

Metab Brain Dis 2021 May 8. Epub 2021 May 8.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Mucolipidosis type IV (MLIV; OMIM 252,650) is an autosomal recessive lysosomal disorder caused by mutations in MCOLN1. MLIV causes psychomotor impairment and progressive vision loss. The major hallmarks of postnatal brain MRI are hypomyelination and thin corpus callosum. Read More

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Oral Administration of Gintonin Protects the Brains of Mice against A-Induced Alzheimer Disease Pathology: Antioxidant and Anti-Inflammatory Effects.

Oxid Med Cell Longev 2021 16;2021:6635552. Epub 2021 Apr 16.

Division of Life Science and Applied Life Science (BK21 FOUR), College of Natural Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea.

The study was aimed at analyzing the protective effects of gintonin in an amyloid beta- (A-) induced Alzheimer's disease (AD) mouse model. For the development of the A-induced AD mouse model, the amyloid- (A) peptide was stereotaxically injected into the brains of mice. Subsequently, gintonin was administered at a dose of 100 mg/kg/day/per oral (p. Read More

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Tau immunotherapy is associated with glial responses in FTLD-tau.

Acta Neuropathol 2021 May 5. Epub 2021 May 5.

Translational Neuropathology Research Laboratory, Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, 613A Stellar Chance Laboratories, 422 Curie Blvd, Philadelphia, PA, 19104, USA.

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neuropathologic subtypes of frontotemporal lobar degeneration with tau inclusions (FTLD-tau), primary tauopathies in which intracellular tau aggregation contributes to neurodegeneration. Gosuranemab (BIIB092) is a humanized monoclonal antibody that binds to N-terminal tau. While Gosuranemab passive immunotherapy trials for PSP failed to demonstrate clinical benefit, Gosuranemab reduced N-terminal tau in the cerebrospinal fluid of transgenic mouse models and PSP patients. Read More

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Effects of Wnt5a overexpression in spinal cord injury.

J Cell Mol Med 2021 May 3. Epub 2021 May 3.

Laboratory of Molecular Neurology, Hospital Nacional de Parapléjicos, Toledo, Spain.

Accordingly to its known function in corticospinal tract (CST) developmental growth, previous reports have shown an inhibitory role of Wnt5a in CST regeneration after spinal cord injury (SCI). Interestingly, it has been subsequently demonstrated that Wnt5a also modulates the developmental growth of non-CST axons and that different Wnt5a receptors are expressed in neurons, oligodendrocytes, NG2+ glial precursors and reactive microglia/macrophages and astrocytes after SCI. However, the role of Wnt5a in the response of these cell types, in the regeneration of non-CST axons and in functional recovery after SCI is currently unknown. Read More

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Isolation of Adult Human Astrocyte Populations from Fresh-frozen Cortex using Fluorescence-Activated Nuclei Sorting.

J Vis Exp 2021 Apr 16(170). Epub 2021 Apr 16.

Department of Pathology, Icahn School of Medicine at Mount Sinai; Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai;

The complexity of human astrocytes remains poorly defined in primary human tissue, requiring better tools for their isolation and molecular characterization. Fluorescence-activated nuclei sorting (FANS) can be used to successfully isolate and study human neuronal nuclei (NeuN+) populations from frozen archival tissue, thereby avoiding problems associated with handling fresh tissue. However, efforts to similarly isolate astroglia from the non-neuronal (NeuN-) element are lacking. Read More

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Protection of the neurovascular unit from calcium-related ischemic injury by linalyl acetate.

Chin J Physiol 2021 Mar-Apr;64(2):88-96

Department of Basic Nursing Science, School of Nursing; BK21 FOUR Program of Transdisciplinary Major in Learning Health Systems, Graduate School, Korea University, Seoul, Republic of Korea.

Calcium-related ischemic injury (CRII) can damage cells of the neurovascular unit (NVU). Here, we investigate the protective effects of linalyl acetate (LA) against CRII-induced NVU damage and evaluate the underlying mechanisms. The protective effects of LA in cell lines representative of NVU components (BEND, SH-SY5Y, BV2, and U373 cells) were evaluated following exposure to oxygen-glucose deprivation/reoxygenation alone (OGD/R-only) or OGD/R in the presence of 5 mM extracellular calcium ([Ca]) to mimic CRII. Read More

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Mycobacterium tuberculosis causes a leaky blood-brain barrier and neuroinflammation in the prefrontal cortex and cerebellum regions of infected mice offspring.

Int J Dev Neurosci 2021 May 1. Epub 2021 May 1.

Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of Kwazulu Natal, Durban, South Africa.

The maternal system's exposure to pathogens influences foetal brain development through the influx of maternal cytokines and activation of the foetal immune status to a persistent inflammatory state characterised by glia cell activation. Neuroinflammation influences the blood-brain barrier's (BBB) permeability allowing peripheral immune cell trafficking into the brain. Mycobacterium tuberculosis (Mtb) is a pathogen that causes Tuberculosis (TB), a global pandemic responsible for health and economic burdens. Read More

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Microglia Specific Drug Targeting Using Natural Products for the Regulation of Redox Imbalance in Neurodegeneration.

Front Pharmacol 2021 13;12:654489. Epub 2021 Apr 13.

Biochemistry and Molecular Biology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi, India.

Microglia, a type of innate immune cell of the brain, regulates neurogenesis, immunological surveillance, redox imbalance, cognitive and behavioral changes under normal and pathological conditions like Alzheimer's, Parkinson's, Multiple sclerosis and traumatic brain injury. Microglia produces a wide variety of cytokines to maintain homeostasis. It also participates in synaptic pruning and regulation of neurons overproduction by phagocytosis of neural precursor cells. Read More

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Alternative Targets to Fight Alzheimer's Disease: Focus on Astrocytes.

Biomolecules 2021 Apr 19;11(4). Epub 2021 Apr 19.

Department of Physiology and Pharmacology "Vittorio Erspamer", SAPIENZA University of Rome-P.le A. Moro, 5, 00185 Rome, Italy.

The available treatments for patients affected by Alzheimer's disease (AD) are not curative. Numerous clinical trials have failed during the past decades. Therefore, scientists need to explore new avenues to tackle this disease. Read More

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Chemogenetic Activation of CX3CR1-Expressing Spinal Microglia Using Gq-DREADD Elicits Mechanical Allodynia in Male Mice.

Cells 2021 Apr 12;10(4). Epub 2021 Apr 12.

Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama City, Wakayama 641-0012, Japan.

It is important to investigate the sex-dependent roles of microglia in pain hypersensitivity as reactive microglia within the spinal dorsal horn (DH) have been reported to be pivotal in neuropathic pain induction in male rodents upon nerve injury. Here, we aimed at determining the role of sex differences in the behavioral and functional outcomes of the chemogenetic activation of spinal microglia using Gq-designer receptors exclusively activated by designer drugs (Gq-DREADD) driven by the microglia-specific Cx3cr1 promoter. CAG-LSL-human Gq-coupled M3 muscarinic receptors (hM3Dq)-DREADD mice were crossed with CX3C chemokine receptor 1 (CX3CR1)-Cre mice, and immunohistochemistry images revealed that hM3Dq was selectively expressed on Iba1 microglia, but not on astrocytes and neurons. Read More

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Neuroinflammatory Response to TNFα and IL1β Cytokines Is Accompanied by an Increase in Glycolysis in Human Astrocytes In Vitro.

Int J Mol Sci 2021 Apr 14;22(8). Epub 2021 Apr 14.

Department of Biomedical Sciences, University of Lausanne, CH-1005 Lausanne, Switzerland.

Astrogliosis has been abundantly studied in rodents but relatively poorly in human cells due to limited access to the brain. Astrocytes play important roles in cerebral energy metabolism, and are also key players in neuroinflammation. Astroglial metabolic and inflammatory changes as a function of age have been reported, leading to the hypothesis that mitochondrial metabolism and inflammatory responses are interconnected in supporting a functional switch of astrocytes from neurotrophic to neurotoxic. Read More

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Endothelin ET Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders.

Authors:
Yutaka Koyama

Int J Mol Sci 2021 Apr 21;22(9). Epub 2021 Apr 21.

Laboratory of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyama-Kita Higashinada, Kobe 668-8558, Japan.

In brain disorders, reactive astrocytes, which are characterized by hypertrophy of the cell body and proliferative properties, are commonly observed. As reactive astrocytes are involved in the pathogenesis of several brain disorders, the control of astrocytic function has been proposed as a therapeutic strategy, and target molecules to effectively control astrocytic functions have been investigated. The production of brain endothelin-1 (ET-1), which increases in brain disorders, is involved in the pathophysiological response of the nervous system. Read More

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Reactive astrocytes facilitate vascular repair and remodeling after stroke.

Cell Rep 2021 Apr;35(4):109048

Institute for Neuroscience, University of Texas at Austin, Austin, TX 78712, USA; Department of Psychology, University of Texas at Austin, Austin, TX 78712, USA.

Brain injury causes astrocytes to assume a reactive state that is essential for early tissue protection, but how reactive astrocytes affect later reparative processes is incompletely understood. In this study, we show that reactive astrocytes are crucial for vascular repair and remodeling after ischemic stroke in mice. Analysis of astrocytic gene expression data reveals substantial activation of transcriptional programs related to vascular remodeling after stroke. Read More

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Blocking microglial activation of reactive astrocytes is neuroprotective in models of Alzheimer's disease.

Acta Neuropathol Commun 2021 Apr 26;9(1):78. Epub 2021 Apr 26.

Russell H, Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

Alzheimer's disease (AD) is the most common cause of age-related dementia. Increasing evidence suggests that neuroinflammation mediated by microglia and astrocytes contributes to disease progression and severity in AD and other neurodegenerative disorders. During AD progression, resident microglia undergo proinflammatory activation, resulting in an increased capacity to convert resting astrocytes to reactive astrocytes. Read More

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GLP-1 improves the neuronal supportive ability of astrocytes in Alzheimer's disease by regulating mitochondrial dysfunction via the cAMP/PKA pathway.

Biochem Pharmacol 2021 Apr 22;188:114578. Epub 2021 Apr 22.

School of Pharmacy, Fujian Medical University, Fuzhou 350122, China; Fujian Key Laboratory of Natural Medicine Pharmacology, Fujian Medical University, Fuzhou 350122, China. Electronic address:

The glucagon-like peptide-1 (GLP-1) was shown to have neuroprotective effects in Alzheimer's disease (AD). However, the underlying mechanism remains elusive. Astrocytic mitochondrial abnormalities have been revealed to constitute important pathologies. Read More

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The extracellular matrix as modifier of neuroinflammation and remyelination in multiple sclerosis.

Brain 2021 Apr 23. Epub 2021 Apr 23.

Hotchkiss Brain Institute and the Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, Canada.

Remyelination failure contributes to axonal loss and progression of disability in multiple sclerosis. The failed repair process could be due to ongoing toxic neuroinflammation and to an inhibitory lesion microenvironment that prevents recruitment and/or differentiation of oligodendrocyte progenitor cells into myelin-forming oligodendrocytes. The extracellular matrix molecules deposited into lesions provide both an altered microenvironment that inhibits oligodendrocyte progenitor cells, and a fuel that exacerbates inflammatory responses within lesions. Read More

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The Emerging Role of the Interplay Among Astrocytes, Microglia, and Neurons in the Hippocampus in Health and Disease.

Front Aging Neurosci 2021 6;13:651973. Epub 2021 Apr 6.

Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.

For over a century, neurons have been considered the basic functional units of the brain while glia only elements of support. Activation of glia has been long regarded detrimental for survival of neurons but more it appears that this is not the case in all circumstances. In this review, we report and discuss the recent literature on the alterations of astrocytes and microglia during inflammaging, the low-grade, slow, chronic inflammatory response that characterizes normal brain aging, and in acute inflammation. Read More

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P2X Receptors in Neurodegeneration: Potential Therapeutic Applications From Basic to Clinical Approaches.

Front Cell Neurosci 2021 6;15:617036. Epub 2021 Apr 6.

Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States.

Purinergic receptors play important roles in central nervous system (CNS), where the bulk of these receptors are implicated in neuroinflammatory responses and regulation of cellular function of neurons, microglial and astrocytes. Within the P2X receptor family, P2X receptor is generally known for its inactivity in normal conditions and activation by moderately high concentrations (>100 μM) of extracellular adenosine 5'-triphosphate (ATP) released from injured cells as a result of brain injury or pathological conditions. Activation of P2XR contributes to the activation and proliferation of microglia and directly contribute to neurodegeneration by provoking microglia-mediated neuronal death, glutamate-mediated excitotoxicity, and NLRP3 inflammasome activation that results in initiation, maturity and release of the pro-inflammatory cytokines and generation of reactive oxygen and nitrogen species. Read More

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Astroglial tracer BU99008 detects multiple binding sites in Alzheimer's disease brain.

Mol Psychiatry 2021 Apr 23. Epub 2021 Apr 23.

Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.

With reactive astrogliosis being established as one of the hallmarks of Alzheimer's disease (AD), there is high interest in developing novel positron emission tomography (PET) tracers to detect early astrocyte reactivity. BU99008, a novel astrocytic PET ligand targeting imidazoline-2 binding sites (IBS) on astrocytes, might be a suitable candidate. Here we demonstrate for the first time that BU99008 could visualise reactive astrogliosis in postmortem AD brains and propose a multiple binding site [Super-high-affinity (SH), High-affinity (HA) and Low-affinity (LA)] model for BU99008, IBS specific ligands (2-BFI and BU224) and deprenyl in AD and control (CN) brains. Read More

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Barcoded viral tracing of single-cell interactions in central nervous system inflammation.

Science 2021 04;372(6540)

Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC H2X 0A9, Canada.

Cell-cell interactions control the physiology and pathology of the central nervous system (CNS). To study astrocyte cell interactions in vivo, we developed rabies barcode interaction detection followed by sequencing (RABID-seq), which combines barcoded viral tracing and single-cell RNA sequencing (scRNA-seq). Using RABID-seq, we identified axon guidance molecules as candidate mediators of microglia-astrocyte interactions that promote CNS pathology in experimental autoimmune encephalomyelitis (EAE) and, potentially, multiple sclerosis (MS). Read More

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MiR-30a-5p Regulates GLT-1 Function via a PKCα-Mediated Ubiquitin Degradation Pathway in a Mouse Model of Parkinson's Disease.

ACS Chem Neurosci 2021 May 21;12(9):1578-1592. Epub 2021 Apr 21.

Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.

Glutamate excitotoxicity is caused by dysfunctional glutamate transporters and plays an important role in the pathogenesis of Parkinson's disease (PD); however, the mechanisms that underlie the regulation of glutamate transporters in PD are still not fully elucidated. MicroRNAs(miRNA), which are abundant in astrocytes and neurons, have been reported to play key roles in regulating the translation of glutamate-transporter mRNA. In this study, we hypothesized that the miR-30a-5p contributes to the pathogenesis of PD by regulating the ubiquitin-mediated degradation of glutamate transporter 1 (GLT-1). Read More

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Ginkgolide B‑induced AMPK pathway activation protects astrocytes by regulating endoplasmic reticulum stress, oxidative stress and energy metabolism induced by Aβ1‑42.

Mol Med Rep 2021 Jun 21;23(6). Epub 2021 Apr 21.

School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, P.R. China.

Ginkgolide B (GB), the diterpenoid lactone compound isolated from the extracts of leaves, significantly improves cognitive impairment, but its potential pharmacological effect on astrocytes induced by β‑amyloid (Aβ) remains to be elucidated. The present study aimed to investigate the protective effect and mechanism of GB on astrocytes with Aβ‑induced apoptosis in Alzheimer's disease (AD). Astrocytes obtained from Sprague Dawley rats were randomly divided into control, Aβ, GB and GB + compound C groups. Read More

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Lack of the peroxiredoxin 6 gene causes impaired spatial memory and abnormal synaptic plasticity.

Mol Brain 2021 04 19;14(1):72. Epub 2021 Apr 19.

Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.

Peroxiredoxin 6 (PRDX6) is expressed dominantly in the astrocytes and exerts either neuroprotective or neurotoxic effects in the brain. Although PRDX6 can modulate several signaling cascades involving cognitive functions, its physiological role in spatial memory has not been investigated yet. This study aims to explore the function of the Prdx6 gene in spatial memory formation and synaptic plasticity. Read More

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Instructive roles of astrocytes in hippocampal synaptic plasticity: neuronal activity-dependent regulatory mechanisms.

FEBS J 2021 Apr 17. Epub 2021 Apr 17.

Division of Life Science, The Hong Kong University of Science and Technology, China.

In the adult hippocampus, synaptic plasticity is important for information processing, learning, and memory encoding. Astrocytes, the most common glial cells, play a pivotal role in the regulation of hippocampal synaptic plasticity. While astrocytes were initially described as a homogenous cell population, emerging evidence indicates that in the adult hippocampus, astrocytes are highly heterogeneous and can differentially respond to changes in neuronal activity in a subregion-dependent manner to actively modulate synaptic plasticity. Read More

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Calcium-dependent cytosolic phospholipase A activation is implicated in neuroinflammation and oxidative stress associated with ApoE4.

Mol Neurodegener 2021 04 16;16(1):26. Epub 2021 Apr 16.

Departments of Medicine and Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Background: Apolipoprotein E4 (APOE4) is associated with a greater response to neuroinflammation and the risk of developing late-onset Alzheimer's disease (AD), but the mechanisms for this association are not clear. The activation of calcium-dependent cytosolic phospholipase A (cPLA2) is involved in inflammatory signaling and is elevated within the plaques of AD brains. The relation between APOE4 genotype and cPLA2 activity is not known. Read More

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Orthopedic surgery-induced cognitive dysfunction is mediated by CX3CL1/R1 signaling.

J Neuroinflammation 2021 Apr 15;18(1):93. Epub 2021 Apr 15.

Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Background: Postoperative pain is a common phenomenon after surgery and is closely associated with the development of postoperative cognitive dysfunction (POCD). Persistent pain and systemic inflammation caused by surgery have been suggested as key factors for the development of POCD. Fractalkine (CX3CL1) and its receptor, the CX3C chemokine receptor 1 (CX3CR1), are known to play a key role in pain and inflammation signaling pathways. Read More

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