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Inflammasome microglia

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https://www.readbyqxmd.com/read/28318352/the-role-of-nlrp3-casp1-in-inflammasome-mediated-neuroinflammation-and-autophagy-dysfunction-in-manganese-induced-hippocampal-dependent-impairment-of-learning-and-memory-ability
#1
Diya Wang, Jianbin Zhang, Wenkai Jiang, Zipeng Cao, Fang Zhao, Tongjian Cai, Michael Aschner, Wenjing Luo
Central nervous system (CNS) inflammation and autophagy dysfunction are known to be involved in the pathology of neurodegenerative diseases. Manganese (Mn), a neurotoxic metal, has the potential to induce microglia-mediated neuroinflammation as well as autophagy dysfunction. NLRP3 (NLR family, pyrin domain containing 3)- CASP1 (caspase 1) inflammasome-mediated neuroinflammation in microglia has specific relevance to neurological diseases. However, the mechanism driving these phenomena remains poorly understood...
February 27, 2017: Autophagy
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#2
Elena K Fetisova, Boris V Chernyak, Galina A Korshunova, Maria S Muntyan, Vladimir P Skulachev
BACKGROUND: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28270571/hiv-1-tat-primes-and-activates-microglial-nlrp3-inflammasome-mediated-neuroinflammation
#3
Ernest T Chivero, Ming-Lei Guo, Palsamy Periyasamy, Ke Liao, Shannon E Callen, Shilpa Buch
Neuroinflammation associated with HIV-1 infection is a problem affecting ∼50% of HIV-infected individuals. NLRP3 inflammasome has been implicated in HIV-induced microglial activation, but the mechanism(s) remain unclear. Since HIV-Tat continues to be present despite antiretroviral therapy and activates NF-kB, we hypothesized that Tat could prime the NLRP3 inflammasome. We found a dose- and time-dependent induction of NLRP3 expression in microglia exposed to Tat compared with control. Tat exposure also time-dependently increased the mature caspase-1 and IL-1β levels and enhanced the IL-1β secretion...
March 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28255908/nlrp3-inflammasome-inhibitor-ameliorates-amyloid-pathology-in-a-mouse-model-of-alzheimer-s-disease
#4
Jun Yin, Fanpeng Zhao, Jeremy E Chojnacki, Jacob Fulp, William L Klein, Shijun Zhang, Xiongwei Zhu
The activation of the NLRP3 inflammasome signaling pathway plays an important role in the neuroinflammation in Alzheimer's disease (AD). In this study, we investigated the effects of JC-124, a rationally designed NLRP3 inflammasome inhibitor, on AD-related deficits in CRND8 APP transgenic mice (TgCRND8). We first demonstrated increased formation and activation of NLRP3 inflammasome in TgCRND8 mice compared to non-transgenic littermate controls, which was inhibited by the treatment with JC-124. Importantly, JC-124 treatment led to decreased levels of Aβ deposition and decreased levels of soluble and insoluble Aβ1-42 in the brain of CRND8 mice which was accompanied by reduced β-cleavage of APP, reduced activation of microglia but enhanced astrocytosis...
March 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28213267/ferulic-acid-inhibits-neuro-inflammation-in-mice-exposed-to-chronic-unpredictable-mild-stress
#5
Ya-Min Liu, Ji-Duo Shen, Li-Ping Xu, Han-Bing Li, Yu-Cheng Li, Li-Tao Yi
Ferulic acid is a hydroxycinnamic acid that widely presents in plant cell wall components. It has been demonstrated that ferulic acid can attenuate depressive-like behaviors in both forced swimming test and tail suspension test. Considering that depression is an inflammatory related mental disease, our present study was aimed to investigate the role of ferulic acid in the regulation of microglia activation, pro-inflammatory cytokines, nuclear factor kappa B (NF-κB) and nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome in mice exposed to chronic unpredictable mild stress (CUMS)...
February 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28164443/low-level-light-emitting-diode-led-therapy-suppresses-inflammasome-mediated-brain-damage-in-experimental-ischemic-stroke
#6
Hae In Lee, Sae-Won Lee, Nam Gyun Kim, Kyoung-Jun Park, Byung Tae Choi, Yong-Il Shin, Hwa Kyoung Shin
Use of photostimulation including low-level light emitting diode (LED) therapy has broadened greatly in recent years because it is compact, portable, and easy to use. Here, the effects of photostimulation by LED (610 nm) therapy on ischemic brain damage was investigated in mice in which treatment started after a stroke in a clinically relevant setting. The mice underwent LED therapy (20 min) twice a day for 3 days, commencing at 4 hours post-ischemia. LED therapy group generated a significantly smaller infarct size and improvements in neurological function based on neurologic test score...
February 6, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28159556/activated-microglia-trigger-inflammasome-activation-and-lysosomal-destabilization-in-human-rpe-cells
#7
Christopher Nebel, Alexander Aslanidis, Khalid Rashid, Thomas Langmann
Activation of the innate immune system plays a major role in retinal degenerative diseases including age-related macular degeneration (AMD). In this study, we investigated whether reactive microglia trigger and sustain NLRP3 inflammasome activation in human retinal pigment epithelium (ARPE-19) cells. Specifically, we analyzed the potential of cell culture supernatants from lipopolysaccharide (LPS)-stimulated human microglia in combination with the lysosomal destabilization agent Leu-Leu-O-Me (LLOMe) to activate the inflammasome in ARPE-19 cells...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28129888/alzheimer-s-disease-innate-immunity-gone-awry
#8
Theodore B VanItallie
Inflammation is an immune activity designed to protect the host from pathogens and noxious agents. In its low-intensity form, presence of an inflammatory process must be inferred from appropriate biomarkers. Occult neuroinflammation is not just secondary to Alzheimer's disease (AD) but may contribute to its pathogenesis and promote its progression. A leaky blood-brain barrier (BBB) has been observed in early AD and may play a role in its initiation and development. Studies of the temporal evolution of AD's biomarkers have shown that, in AD, the brain's amyloid burden correlates poorly with cognitive decline...
April 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28011393/astragaloside-iv-attenuates-cognitive-impairments-induced-by-transient-cerebral-ischemia-and-reperfusion-in-mice-via-anti-inflammatory-mechanisms
#9
Min Li, Hongyan Li, Fang Fang, Xueyang Deng, Shiping Ma
Astragaloside IV (AS-IV) is the main active component isolated from the traditional Chinese medicinal herb Astragalus membranaceus. Studies have demonstrated that AS-IV has neuroprotective effects in cerebral ischemic models. In this study, we aimed to investigate the effects of AS-IV on memory impairment induced by transient cerebral ischemia and reperfusion in mice, as well as the associated signaling mechanisms. Severe memory deficits were induced by bilateral common carotid artery occlusion (BCCAO) in mice as indicated in the Morris water maze test in this study...
February 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28009077/inflammasomes-as-therapeutic-targets-for-alzheimer-s-disease
#10
Claire S White, Catherine B Lawrence, David Brough, Jack Rivers-Auty
Alzheimer's disease is the most common form of progressive dementia, typified initially by short term memory deficits which develop into a dramatic global cognitive decline. The classical hall marks of Alzheimer's disease include the accumulation of amyloid oligomers and fibrils, and the intracellular formation of neurofibrillary tangles of hyperphosphorylated tau. It is now clear that inflammation also plays a central role in the pathogenesis of the disease through a number of neurotoxic mechanisms. Microglia are the key immune regulators of the CNS which detect amyloidopathy through cell surface and cytosolic pattern recognition receptors (PRRs) and respond by initiating inflammation through the secretion of cytokines such as interleukin-1β (IL-1β)...
March 2017: Brain Pathology
https://www.readbyqxmd.com/read/28003153/inhibiting-the-nlrp3-inflammasome-with-mcc950-promotes-non-phlogistic-clearance-of-amyloid-%C3%AE-and-cognitive-function-in-app-ps1-mice
#11
C Dempsey, A Rubio Araiz, K J Bryson, O Finucane, C Larkin, E L Mills, A A B Robertson, M A Cooper, L A J O'Neill, M A Lynch
Activation of the inflammasome is implicated in the pathogenesis of an increasing number of inflammatory diseases, including Alzheimer's disease (AD). Research reporting inflammatory changes in post mortem brain tissue of individuals with AD and GWAS data have convincingly demonstrated that neuroinflammation is likely to be a key driver of the disease. This, together with the evidence that genetic variants in the NLRP3 gene impact on the risk of developing late-onset AD, indicates that targetting inflammation offers a therapeutic opportunity...
December 18, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27846628/minocycline-suppresses-nlrp3-inflammasome-activation-in-experimental-ischemic-stroke
#12
Yunnan Lu, Guodong Xiao, Weifeng Luo
OBJECTIVE: Minocycline, a tetracycline antibiotic, has shown anti-inflammatory effects in cerebral ischemia and neurodegenerative disease; however, the molecular mechanisms underlying this effect have not been clearly identified. Since NLRP3 inflammasome activation controls the maturation and release of proinflammatory cytokines, especially interleukin-1β (IL-1β) and IL-18 in ischemia stroke, we suppose that minocycline may be involved in the regulation of NLRP3 inflammasome activation...
2016: Neuroimmunomodulation
https://www.readbyqxmd.com/read/27831552/knockout-of-ccr2-alleviates-photoreceptor-cell-death-in-rodent-retina-exposed-to-chronic-blue-light
#13
Zizhong Hu, Yi Zhang, Junling Wang, Pingan Mao, Xuehua Lv, Songtao Yuan, Zhengru Huang, Yuzhi Ding, Ping Xie, Qinghuai Liu
Age-related macular degeneration (AMD), the leading cause of visual loss after the age of 60 years, is a degenerative retinal disease involving a variety of environmental and hereditary factors. Although it has been implicated that immune system is involved in the disease progression, the exact role that microglia has is still unclear. Here we demonstrated that knockout of Ccr2 gene could alleviate photoreceptor cell death in mice retinas exposed to chronic blue light. In Ccr2(-/-) mice, a damaged microglia recruitment was shown in retina and this could protect the visual function in electroretinogram and alleviate the photoreceptor apoptosis, which thus helped attenuate the blue light-induced retinopathy...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27797173/dipeptidyl-vinyl-sulfone-as-a-novel-chemical-tool-to-inhibit-hmgb1-nlrp3-inflammasome-and-inflamma-mirs-in-a%C3%AE-mediated-microglial-inflammation
#14
Ana S Falcão, Luís A R Carvalho, Gonçalo Lidónio, Ana R Vaz, Susana D Lucas, Rui Moreira, Dora Brites
Rapid microglial activation and associated inflammatory pathways contribute to immune-defense and tissue repair in the central nervous system (CNS). However, persistent activation of these cells will ultimately result in vast production of pro-inflammatory mediators and other neurotoxic factors, which may induce neuronal damage and contribute to chronic neurodegenerative diseases, as Alzheimer's disease (AD). Therefore, small molecules with immunomodulatory effects on microglia may be considered as potential tools to counteract their proinflammatory phenotype and neuroimmune dysregulation in such disorders...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27769904/learned-helplessness-activates-hippocampal-microglia-in-rats-a-potential-target-for-the-antidepressant-imipramine
#15
Masaaki Iwata, Hisahito Ishida, Koichi Kaneko, Yukihiko Shirayama
An accumulating body of evidence has demonstrated that inflammation is associated with the pathology of depression. We recently found that psychological stress induces inflammation in the hippocampus of the rat brain through the inflammasome, a component of the innate immune system. Microglia, the resident macrophages in the brain, play a central role in the innate immune system and express inflammasomes; thus, we hypothesized that hippocampal microglia would be key mediators in the development of depression via stress-induced inflammation...
November 2016: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27769021/the-neuroprotection-of-sinomenine-against-ischemic-stroke-in-mice-by-suppressing-nlrp3-inflammasome-via-ampk-signaling
#16
Jing Qiu, Min Wang, Jun Zhang, Qing Cai, Dan Lu, Yansong Li, Yushu Dong, Tianzhi Zhao, Huisheng Chen
Neuroinflammation remains the primary cause of morbidity and mortality in stroke-induced secondary brain injury. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is involved in diverse inflammatory diseases, including cerebral ischemia, and is thus considered an effective therapeutic target. In the present study, we investigated the neuroprotection of Sinomenine (SINO), a potent natural anti-apoptotic and anti-inflammatory molecule, against cerebral ischemia in a mouse model of middle cerebral artery occlusion (MCAO) in vivo and in an oxygen glucose deprivation (OGD)-treated astrocytes/microglia model in vitro...
November 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27742410/baicalein-attenuates-%C3%AE-synuclein-aggregation-inflammasome-activation-and-autophagy-in-the-mpp-treated-nigrostriatal-dopaminergic-system-in-vivo
#17
Kai-Chih Hung, Hui-Ju Huang, Yi-Ting Wang, Anya Maan-Yuh Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Neuroinflammation, oxidative stress, and protein aggregation form a vicious cycle in the pathophysiology of Parkinson's disease (PD); activated microglia is the main location of neuroinflammation. A Chinese medicine book, "Shanghan Lun", known as the "Treatises on Cold damage Diseases" has suggested that Scutellaria baicalensis Georgi is effective in treating CNS diseases. The anti-inflammatory mechanisms of baicalein, a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi, remain to be explored...
December 24, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27726055/hiv-1-viral-protein-r-activates-nlrp3-inflammasome-in-microglia-implications-for-hiv-1-associated-neuroinflammation
#18
Manmeet K Mamik, Elizabeth Hui, William G Branton, Brienne A McKenzie, Jesse Chisholm, Eric A Cohen, Christopher Power
Human Immunodeficiency virus (HIV) enters the brain soon after seroconversion and induces chronic neuroinflammation by infecting and activating brain macrophages. Inflammasomes are cytosolic protein complexes that mediate caspase-1 activation and ensuing cleavage and release of IL-1β and -18 by macrophages. Our group recently showed that HIV-1 infection of human microglia induced inflammasome activation in NLRP3-dependent manner. The HIV-1 viral protein R (Vpr) is an accessory protein that is released from HIV-infected cells, although its effects on neuroinflammation are undefined...
October 10, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/27718173/neuroinflammation-immune-system-and-alzheimer-disease-searching-for-the-missing-link
#19
F Guerriero, C Sgarlata, M Francis, N Maurizi, A Faragli, S Perna, M Rondanelli, M Rollone, G Ricevuti
Due to an increasingly aging population, Alzheimer disease (AD) represents a crucial issue for the healthcare system because of its widespread prevalence and the burden of its care needs. Several hypotheses on AD pathogenesis have been proposed and current therapeutical strategies have shown limited effectiveness. In the last decade, more evidence has supported a role for neuroinflammation and immune system dysregulation in AD. It remains unclear whether astrocytes, microglia and immune cells influence disease onset, progression or both...
October 7, 2016: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/27650785/impact-of-the-innate-immune-response-in-the-actions-of-ethanol-on-the-central-nervous-system
#20
Jorge Montesinos, Silvia Alfonso-Loeches, Consuelo Guerri
The innate immune response in the central nervous system (CNS) participates in both synaptic plasticity and neural damage. Emerging evidence from human and animal studies supports the role of the neuroimmune system response in many actions of ethanol (EtOH) on the CNS. Research studies have shown that alcohol stimulates brain immune cells, microglia, and astrocytes, by activating innate immune receptors Toll-like receptors (TLRs) and NOD-like receptors (inflammasome NLRs) triggering signaling pathways, which culminate in the production of pro-inflammatory cytokines and chemokines that lead to neuroinflammation...
September 21, 2016: Alcoholism, Clinical and Experimental Research
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