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https://www.readbyqxmd.com/read/28811143/nadph-oxidases-as-drug-targets-and-biomarkers-in-neurodegenerative-diseases-what-is-the-evidence
#1
REVIEW
Silvia Sorce, Roland Stocker, Tamara Seredenina, Rikard Holmdahl, Adriano Aguzzi, Adriano Chio, Antoine Depaulis, Freddy Heitz, Peter Olofsson, Tomas Olsson, Venceslas Duveau, Despina Sanoudou, Sara Skosgater, Antonia Vlahou, Dominique Wasquel, Karl-Heinz Krause, Vincent Jaquet
Neurodegenerative disease are frequently characterized by microglia activation and/or leukocyte infiltration in the parenchyma of the central nervous system and at the molecular level by increased oxidative modifications of proteins, lipids and nucleic acids. NADPH oxidases (NOX) emerged as a novel promising class of pharmacological targets for the treatment of neurodegeneration due to their role in oxidant generation and presumably in regulating microglia activation. The unique function of NOX is the generation of superoxide anion (O2(•-)) and hydrogen peroxide (H2O2)...
August 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28804456/lessons-learned-about-neurodegeneration-from-microglia-and-monocyte-depletion-studies
#2
REVIEW
Harald Lund, Melanie Pieber, Robert A Harris
While bone marrow-derived Ly6C(hi) monocytes can infiltrate the central nervous system (CNS) they are developmentally and functionally distinct from resident microglia. Our understanding of the relative importance of these two populations in the distinct processes of pathogenesis and resolution of inflammation during neurodegenerative disorders was limited by a lack of tools to specifically manipulate each cell type. During recent years, the development of experimental cell-specific depletion models has enabled this issue to be addressed...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28801024/understanding-the-role-of-socs-signaling-in-neurodegenerative-diseases-current-and-emerging-concepts
#3
REVIEW
Antonia Cianciulli, Rosa Calvello, Chiara Porro, Teresa Trotta, Maria Antonietta Panaro
Suppressor of cytokine signaling proteins (SOCS) are a family of intracellular cytokine inducible proteins, consisting of eight members. They are involved in the complex control of the inflammatory response through their actions on various signaling pathways, including the JAK/STAT and NF-κB pathways. A series of studies has shown that SOCS proteins are involved in the regulation and progression of immune responses in microglia cells. The accumulated data suggest that modulation of SOCS expression could be a target for drug development aimed at controlling inflammation in the brain...
August 1, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28797292/the-ethanol-extract-of-aquilariae-lignum-ameliorates-hippocampal-oxidative-stress-in-a-repeated-restraint-stress-mouse-model
#4
Hyun-Yong Lee, Jin-Seok Lee, Hyeong-Geug Kim, Won-Yong Kim, Seung-Bae Lee, Yung-Hyun Choi, Chang-Gue Son
BACKGROUND: Chronic stress contributes to the development of brain disorders, such as neurodegenerative and psychiatric diseases. Oxidative damage is well known as a causative factor for pathogenic process in brain tissues. The aim of this study is to evaluate the neuroprotective effect of a 30% ethanol extract of Aquilariae Lignum (ALE) in repeated stress-induced hippocampal oxidative injury. METHODS: Fifty BALB/c male mice (12 weeks old) were randomly divided into five groups (n = 10)...
August 10, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28796285/inhibition-of-histone-deacetylase-1-or-2-reduces-induced-cytokine-expression-in-microglia-through-a-protein-synthesis-independent-mechanism
#5
Benjamin S Durham, Ronald Grigg, Ian C Wood
Histone deacetylase (HDAC) inhibitors prevent neural cell death in in vivo models of cerebral ischaemia, brain injury and neurodegenerative disease. One mechanism by which HDAC inhibitors may do this is by suppressing the excessive inflammatory response of chronically activated microglia. However, the molecular mechanisms underlying this anti-inflammatory effect and the specific HDAC responsible are not fully understood. Recent data from in vivo rodent studies has shown that inhibition of class I HDACs suppresses neuroinflammation and is neuroprotective...
August 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28792282/anti-inflammation-conferred-by-stimulation-of-cd200r1-via-dok1-pathway-in-rat-microglia-after-germinal-matrix-hemorrhage
#6
Zhanhui Feng, Lan Ye, Damon Klebe, Yan Ding, Zhen-Ni Guo, Jerry J Flores, Cheng Yin, Jiping Tang, John H Zhang
CD200 has been reported to be neuroprotective in neurodegenerative diseases. However, the potential protective effects of CD200 in germinal matrix hemorrhage (GMH) have not been investigated. We examined the anti-inflammatory mechanisms of CD200 after GMH. A total of 167 seven-day-old rat pups were used. The time-dependent effect of GMH on the levels of CD200 and CD200 Receptor 1 (CD200R1) was evaluated by western blot. CD200R1 was localized by immunohistochemistry. The short-term (24 h) and long-term (28 days) outcomes were evaluated after CD200 fusion protein (CD200Fc) treatment by neurobehavioral assessment...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28790913/the-dual-role-of-microglia-in-als-mechanisms-and-therapeutic-approaches
#7
REVIEW
Maria Concetta Geloso, Valentina Corvino, Elisa Marchese, Alessia Serrano, Fabrizio Michetti, Nadia D'Ambrosi
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a non-cell autonomous motor neuron loss. While it is generally believed that the disease onset takes place inside motor neurons, different cell types mediating neuroinflammatory processes are considered deeply involved in the progression of the disease. On these grounds, many treatments have been tested on ALS animals with the aim of inhibiting or reducing the pro-inflammatory action of microglia and astrocytes and counteract the progression of the disease...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28790895/brain-metal-distribution-and-neuro-inflammatory-profiles-after-chronic-vanadium-administration-and-withdrawal-in-mice
#8
Oluwabusayo R Folarin, Amanda M Snyder, Douglas G Peters, Funmilayo Olopade, James R Connor, James O Olopade
Vanadium is a potentially toxic environmental pollutant and induces oxidative damage in biological systems including the central nervous system (CNS). Its deposition in brain tissue may be involved in the pathogenesis of certain neurological disorders which after prolonged exposure can culminate into more severe pathology. Most studies on vanadium neurotoxicity have been done after acute exposure but in reality some populations are exposed for a lifetime. This work was designed to ascertain neurodegenerative consequences of chronic vanadium administration and to investigate the progressive changes in the brain after withdrawal from vanadium treatment...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28789997/environmentally-relevant-level-of-aflatoxin-b1-elicits-toxic-pro-inflammatory-response-in-murine-cns-derived-cells
#9
Jalil Mehrzad, Amir Mohammad Malvandi, Mohsen Alipour, Saman Hosseinkhani
Aflatoxin B1 (AFB1) is a well-known member of aflatoxins (AFs) that is considered among highly stable toxic contaminants of food, worldwide. The impact of AFB1 on neural cells and systems has poorly been understood. To assess the cellular effects of AFB1 on brain, we used murine pure primary astrocytes, sub ventricular zone-derived neural precursor cells (NPCs) and microglia cell line (BV2). Cells were exposed separately to environmentally relevant level (20ng/ml) of AFB1 for 1, 2, 3, 6, 12, 24 and 48h in culture...
August 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28777000/quantitative-proteomics-reveal-temporal-proteomic-changes-in-signaling-pathways-during-bv2-mouse-microglial-cell-activation
#10
Jongmin Woo, Dohyun Han, Joseph Inje Wang, Joonho Park, Hyunsoo Kim, Youngsoo Kim
The development of systematic proteomic quantification techniques in systems biology research has enabled one to perform an in-depth analysis of cellular systems. In this study, we have developed a systematic proteomic approach that encompasses the spectrum from global to targeted analysis on a single platform. We have applied this technique to an activated microglia cell system to examine changes in the intracellular and extracellular proteomes. Microglia become activated when their homeostatic microenvironment is disrupted...
August 4, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28774789/impaired-cbs-h2s-signaling-axis-contributes-to-mptp-induced-neurodegeneration-in-a-mouse-model-of-parkinson-s-disease
#11
Yu-Qing Yuan, Ya-Li Wang, Bao-Shi Yuan, Xin Yuan, Xiao-Ou Hou, Jin-Song Bian, Chun-Feng Liu, Li-Fang Hu
Hydrogen sulfide (H2S), a novel neuromodulator, is linked to the pathogenesis of several neurodegenerative disorders. Exogenous application of H2S exerts neuroprotection via anti-inflammation and anti-oxidative stress in animal and cellular models of Parkinson's disease (PD). However, the role of endogenous H2S and the contribution of its various synthases in PD remain unclear. In the present study, we found a decline of plasma and striatal sulfide level in 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mouse model...
August 1, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28771234/aav5-mihtt-gene-therapy-demonstrates-suppression-of-mutant-huntingtin-aggregation-and-neuronal-dysfunction-in-a-rat-model-of-huntington-s-disease
#12
J Miniarikova, V Zimmer, R Martier, C C Brouwers, C Pythoud, K Richetin, M Rey, J Lubelski, M M Evers, S J van Deventer, H Petry, N Déglon, P Konstantinova
Huntington's disease (HD) is a fatal progressive neurodegenerative disease caused by a mutation in the huntingtin (HTT) gene. To date, there is no treatment to halt or reverse the course of HD. Lowering of either total or only the mutant HTT expression is expected to have therapeutic benefit. This can be achieved by engineered micro (mi)RNAs targeting HTT transcripts and delivered by an adeno-associated viral (AAV) vector. We have previously showed a miHTT construct to induce total HTT knock-down in Hu128/21 HD mice, while miSNP50T and miSNP67T constructs induced allele-selective HTT knock-down in vitro...
August 3, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28758903/transcriptional-control-of-microglia-phenotypes-in-health-and-disease
#13
Inge R Holtman, Dylan Skola, Christopher K Glass
Microglia are the main resident macrophage population of the CNS and perform numerous functions required for CNS development, homeostasis, immunity, and repair. Many lines of evidence also indicate that dysregulation of microglia contributes to the pathogenesis of neurodegenerative and behavioral diseases. These observations provide a compelling argument to more clearly define the mechanisms that control microglia identity and function in health and disease. In this Review, we present a conceptual framework for how different classes of transcription factors interact to select and activate regulatory elements that control microglia development and their responses to internal and external signals...
July 31, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28757373/anti-inflammatory-mechanism-of-galangin-in-lipopolysaccharide-stimulated-microglia-critical-role-of-ppar-%C3%AE-signaling-pathway
#14
Min-Ji Choi, Eun-Jung Lee, Jin-Sun Park, Su-Nam Kim, Eun-Mi Park, Hee-Sun Kim
Since microglia-associated neuroinflammation plays a pivotal role in the progression of neurodegenerative diseases, controlling microglial activation has been suggested as a potential therapeutic strategy. Here, we investigated the anti-inflammatory effects of galangin (3,5,7-trihydroxyflavone) in microglia and analyzed the underlying molecular mechanisms. Galangin inhibited the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines and enhanced the expression of anti-inflammatory interleukin (IL)-10 in lipopolysaccharide (LPS)-stimulated BV2 microglia...
July 28, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28755749/increased-expression-of-m1-and-m2-phenotypic-markers-in-isolated-microglia-after-four-day-binge-alcohol-exposure-in-male-rats
#15
Hui Peng, Chelsea R Geil Nickell, Kevin Y Chen, Justin A McClain, Kimberly Nixon
Microglia activation and neuroinflammation are common features of neurodegenerative conditions, including alcohol use disorders (AUDs). When activated, microglia span a continuum of diverse phenotypes ranging from classically activated, pro-inflammatory (M1) microglia/macrophages to alternatively activated, growth-promoting (M2) microglia/macrophages. Identifying microglia phenotypes is critical for understanding the role of microglia in the pathogenesis of AUDs. Therefore, male rats were gavaged with 25% (w/v) ethanol or isocaloric control diet every 8 h for 4 days and sacrificed at 0, 2, 4, and 7 days after alcohol exposure (e...
August 2017: Alcohol
https://www.readbyqxmd.com/read/28754560/correlation-of-cellular-factors-and-differential-scrapie-prion-permissiveness-in-ovine-microglia
#16
Kelcey D Dinkel, David A Schneider, Juan F Muñoz-Gutiérrez, Valerie R McElliott, James B Stanton
Prion diseases are fatal neurodegenerative disorders by which the native cellular prion protein (PrP(C)) is misfolded into an accumulating, disease-associated isoform (PrP(D)). To improve the understanding of prion pathogenesis and develop effective treatments, it is essential to elucidate factors contributing to cellular permissiveness. We previously isolated five clones from an immortalized subline of ovine microglia, two of which had demonstrated differential permissiveness to a natural isolate of sheep scrapie and distinct transcriptomic profiles...
July 25, 2017: Virus Research
https://www.readbyqxmd.com/read/28752628/intranasal-delivery-of-dexamethasone-efficiently-controls-lps-induced-murine-neuroinflammation
#17
Gabriela Meneses, Gohar Gevorkian, Alejandra Florentino, Marcel Alberto Bautista, Alejandro Espinosa, Gonzalo Acero, Georgina Díaz, Agnes Fleury, Ivan Nicolás Pérez Osorio, Adriana Del Rey, Gladis Fragoso, Edda Sciutto, Hugo Besedosky
Neuroinflammation is the hallmark of several infectious and neurodegenerative diseases. Synthetic glucocorticoids (GCs) are the first-line immunosuppressive drugs used for controlling neuroinflammation. A delayed diffusion of GCs molecules and the high systemic doses required for brain-specific targeting lead to severe undesirable effects, particularly when lifelong treatment is required. Therefore, there is an urgent need for improving this current therapeutic approach. The intranasal (IN) route is being increasingly employed for drug delivery to the brain via the olfactory system...
July 28, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28752032/potassium-2-l-hydroxypentyl-benzoate-attenuates-neuroinflammatory-responses-and-upregulates-heme-oxygenase-1-in-systemic-lipopolysaccharide-induced-inflammation-in-mice
#18
Chunyang Zhao, Weizhen Hou, Hui Lei, Longjian Huang, Shan Wang, Dandan Cui, Changhong Xing, Xiaoliang Wang, Ying Peng
A neuroinflammatory response is commonly involved in the progression of many neurodegenerative diseases. Potassium 2-(1-hydroxypentyl)-benzoate (PHPB), a novel neuroprotective compound, has shown promising effects in the treatment of ischemic stroke and Alzheimer׳s disease (AD). In the present study, the anti-inflammatory effects of PHPB were investigated in the plasma and brain of C57BL/6 mice administered a single intraperitoneal (i.p.) injection of lipopolysaccharide (LPS). Levels of iNOS and the cytokines TNFα, IL-1β and IL-10 were elevated in plasma, cerebral cortex and hippocampus after LPS injection and the number of microglia and astrocytes in cortex and hippocampus were increased...
July 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28747667/rna-sequencing-reveals-resistance-of-tlr4-ligand-activated-microglial-cells-to-inflammation-mediated-by-the-selective-jumonji-h3k27-demethylase-inhibitor
#19
Amitabh Das, Sarder Arifuzzaman, Taeho Yoon, Sun Hwa Kim, Jin Choul Chai, Young Seek Lee, Kyoung Hwa Jung, Young Gyu Chai
Persistent microglial activation is associated with the production and secretion of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27 (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was proven to exert immunosuppressive activities in macrophages. However, a genome-wide search for GSK-J4 molecular targets has not been undertaken in microglia. To study the immuno-modulatory effects of GSK-J4 at the transcriptomic level, triplicate RNA sequencing and quantitative real-time PCR analyses were performed with resting, GSK-J4-, LPS- and LPS + GSK-J4-challenged primary microglial (PM) and BV-2 microglial cells...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28747388/neuronal-p2x7-receptors-revisited-do-they-really-exist
#20
Peter Illes, Tahir Muhammad Khan, Patrizia Rubini
P2X7 receptors (Rs) constitute a subclass of ATP-sensitive ionotropic receptors (P2X1-P2X7). P2X7Rs have many distinguishing features, mostly based on their long intracellular C terminus regulating trafficking to the cell membrane, protein-protein interactions, and post-translational modification. Their C-terminal tail is especially important in enabling the transition from the nonselective ion channel mode to a membrane pore allowing the passage of large molecules. There is an ongoing dispute on the existence of neuronal P2X7Rs with consequences for our knowledge on their involvement in neuroinflammation, aggravating stroke, temporal lobe epilepsy, neuropathic pain, and various neurodegenerative diseases...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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