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https://www.readbyqxmd.com/read/29789522/a20-critically-controls-microglia-activation-and-inhibits-inflammasome-dependent-neuroinflammation
#1
Sofie Voet, Conor Mc Guire, Nora Hagemeyer, Arne Martens, Anna Schroeder, Peter Wieghofer, Carmen Daems, Ori Staszewski, Lieselotte Vande Walle, Marta Joana Costa Jordao, Mozes Sze, Hanna-Kaisa Vikkula, Delphine Demeestere, Griet Van Imschoot, Charlotte L Scott, Esther Hoste, Amanda Gonçalves, Martin Guilliams, Saskia Lippens, Claude Libert, Roos E Vandenbroucke, Ki-Wook Kim, Steffen Jung, Zsuzsanna Callaerts-Vegh, Patrick Callaerts, Joris de Wit, Mohamed Lamkanfi, Marco Prinz, Geert van Loo
Microglia, the mononuclear phagocytes of the central nervous system (CNS), are important for the maintenance of CNS homeostasis, but also critically contribute to CNS pathology. Here we demonstrate that the nuclear factor kappa B (NF-κB) regulatory protein A20 is crucial in regulating microglia activation during CNS homeostasis and pathology. In mice, deletion of A20 in microglia increases microglial cell number and affects microglial regulation of neuronal synaptic function. Administration of a sublethal dose of lipopolysaccharide induces massive microglia activation, neuroinflammation, and lethality in mice with microglia-confined A20 deficiency...
May 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29786072/mptp-driven-nlrp3-inflammasome-activation-in-microglia-plays-a-central-role-in-dopaminergic-neurodegeneration
#2
Eunju Lee, Inhwa Hwang, Sangjun Park, Sujeong Hong, Boreum Hwang, Yoeseph Cho, Junghyun Son, Je-Wook Yu
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the reduction of dopamine levels in the striatum. Although details of the molecular mechanisms underlying dopaminergic neuronal death in PD remain unclear, neuroinflammation is also considered a potent mediator in the pathogenesis and progression of PD. In the present study, we present evidences that microglial NLRP3 inflammasome activation is critical for dopaminergic neuronal loss and the subsequent motor deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29775613/suppression-of-nlrp3-inflammasome-attenuates-stress-induced-depression-like-behavior-in-nlgn3-deficient-mice
#3
Ze-Qun Li, Zhi-Yuan Yan, Bo-Jun Lan, Yi-Qun Dong, Ye Xiong
Depression, regulated by central nervous system (CNS), is a significant inflammatory disorder. Neuroligin3 (NLGN3) has been implicated in brain functions. In the study, a chronic unpredictable mild stress (CUMS) model in wild type (WT) or NLGN3-knockout (KO) mice was established to explore the role of NLGN3 in regulating depression and to reveal the underlying molecular mechanism. The results indicated that NLGN3-knockout markedly reversed the loss of body weight, the reduction of sucrose consumption, the decrease of immobile time in the forced swimming tests (FST) and tail suspension tests (TST) induced by CUMS paradigm...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29774334/a-comparative-study-of-epa-enriched-ethanolamine-plasmalogen-and-epa-enriched-phosphatidylethanolamine-on-a%C3%AE-42-induced-cognitive-deficiency-in-a-rat-model-of-alzheimer-s-disease
#4
Hongxia Che, Qian Li, Tiantian Zhang, Lin Ding, Lingyu Zhang, Haohao Shi, Teruyoshi Yanagita, Changhu Xue, Yaoguang Chang, Yuming Wang
Ethanolamine plasmalogen (pPE), a major phospholipid in neuronal membranes, is specifically reduced in postmortem brains from patients with Alzheimer's disease (AD). The purpose of the present study was to compare the effects of EPA-enriched ethanolamine plasmalogen (EPA-pPE) and EPA-enriched phosphatidylethanolamine (EPA-PE) on cognitive deficiency and illustrate the possible underlying mechanisms. SD rats were divided into four groups including the sham group injected with 0.9% saline and three amyloid-β (Aβ) infusion groups, Aβ42 group, EPA-pPE group and EPA-PE group...
May 18, 2018: Food & Function
https://www.readbyqxmd.com/read/29740969/peripheral-cannabinoid-1-receptor-blockade-mitigates-adipose-tissue-inflammation-via-nlrp3-inflammasome-in-mouse-models-of-obesity
#5
Ji Hye Han, Hanho Shin, Jun Gi Rho, Jung-Eun Kim, Dong Hwee Son, Juhwan Yoon, Yong Jae Lee, Jung-Hyuck Park, Byung Jeong Song, Chang-Sik Choi, Seul Gi Yoon, Il Yong Kim, Eun Kyung Lee, Je Kyung Seong, Ki Woo Kim, Wook Kim
AIMS: Cannabinoid 1 receptor (CB1R) antagonists have been shown to improve insulin resistance and the associated metabolic abnormalities, but their therapeutic development was discontinued due to neuropsychiatric side effects. This study evaluated AJ5018 as the peripherally restricted CB1R antagonist, synthesized by modifying the structure of its brain-penetrant parent compound rimonabant, and analyzed the metabolic parameters and adipose tissue inflammation via NLRP3 inflammasome following chronic treatment of mouse models of obesity with AJ5018...
May 8, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29720937/the-nlrp3-caspase-1-inflammasome-negatively-regulates-autophagy-via-tlr4-trif-in-prion-peptide-infected-microglia
#6
Mengyu Lai, Hao Yao, Syed Zahid Ali Shah, Wei Wu, Di Wang, Ying Zhao, Lu Wang, Xiangmei Zhou, Deming Zhao, Lifeng Yang
Prion diseases are neurodegenerative disorders characterized by the accumulation of misfolded prion protein, spongiform changes in the brain, and brain inflammation as a result of the wide-spread activation of microglia. Autophagy is a highly conserved catabolic process for the clearance of cytoplasmic components, including protein aggregates and damaged organelles; this process also eliminates pathological PrPSc as it accumulates during prion infection. The NALP3 inflammasome is a multiprotein complex that is a component of the innate immune system and is responsible for the release of pro-inflammatory cytokines...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29714132/mir-7-replacement-therapy-in-parkinson-s-disease
#7
Ricardo Titze-de-Almeida, Simoneide Souza Titze-de-Almeida
The present review examines whether the microRNA 7 (miR-7) holds potential for slowing Parkinson's disease (PD) progression. First, the accurate expression of miR-7 allows for the normal development, physiology, and neurogenesis in the central nervous system, also keeping alpha-synuclein (α-Syn) at the physiological level. Second, patients with PD and parkinsonian MPTP-induced animals exhibit a significant decrease of miR-7 in brain areas associated with dopaminergic neurodegeneration. Depletion of miR-7 in the substantia nigra of clinical samples was related to α-Syn accumulation, loss of dopaminergic cells, and reduction of dopamine in the striatum...
April 30, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29710856/nicotine-alters-estrogen-receptor-beta-regulated-inflammasome-activity-and-exacerbates-ischemic-brain-damage-in-female-rats
#8
Nathan D d'Adesky, Juan Pablo de Rivero Vaccari, Pallab Bhattacharya, Marc Schatz, Miguel A Perez-Pinzon, Helen M Bramlett, Ami P Raval
Smoking is a preventable risk factor for stroke and smoking-derived nicotine exacerbates post-ischemic damage via inhibition of estrogen receptor beta (ER-β) signaling in the brain of female rats. ER-β regulates inflammasome activation in the brain. Therefore, we hypothesized that chronic nicotine exposure activates the inflammasome in the brain, thus exacerbating ischemic brain damage in female rats. To test this hypothesis, adult female Sprague-Dawley rats (6⁻7 months old) were exposed to nicotine (4...
April 30, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29685192/the-role-of-alu-derived-rnas-in-alzheimer-s-and-other-neurodegenerative-conditions
#9
Oksana Polesskaya, Evgeniya Kananykhina, Astrid M Roy-Engel, Olga Nazarenko, Irina Kulemzina, Ancha Baranova, Yegor Vassetsky, Max Myakishev-Rempel
Non-coding RNAs have emerged as essential contributors to neuroinflammation. The Alu element is the most abundant potential source of non-coding RNA in the human genome represented by over 1.1 million copies totaling ∼10% of the genome's mass. Accumulation of "Alu RNA" was observed in the brains of individuals with dementia and Creutzfeldt-Jakob disease - a degenerative brain disorder. "Alu RNAs" activate inflammatory pathways and apoptosis in the non-neural cells. In particular, the "Alu RNA" cytotoxicity is suggested as a mechanism in retinal pigment epithelium (RPE), a compartment damaged in the process of age-related macular degeneration...
June 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29665808/critical-role-of-nlrp3-caspase-1-pathway-in-age-dependent-isoflurane-induced-microglial-inflammatory-response-and-cognitive-impairment
#10
Zhi Wang, Shiyu Meng, Lin Cao, Ying Chen, Zhiyi Zuo, Shuling Peng
BACKGROUND: Elderly patients are more likely to suffer from postoperative cognitive dysfunction (POCD) after surgery and anesthesia. Except for declined organ function, the particular pathogenesis of POCD in elderly patients remains unknown. This study is carried out to determine the critical role of the NOD-like receptor protein 3 (NLRP3)-caspase-1 pathway in isoflurane-induced cognitive impairment. METHODS: Young (6-8 months old) and aged (14 months old) healthy male C57BL/6 mice were exposed to 1...
April 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29662437/ketogenic-diet-improves-brain-ischemic-tolerance-and-inhibits-nlrp3-inflammasome-activation-by-preventing-drp1-mediated-mitochondrial-fission-and-endoplasmic-reticulum-stress
#11
Min Guo, Xun Wang, Yanxin Zhao, Qi Yang, Hongyan Ding, Qiang Dong, Xingdong Chen, Mei Cui
Background : Neuroprotective effects of ketogenic diets (KD) have been reported in stroke models, and nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome has also been implicated in the pathogenesis of stroke. This study aimed to investigate the effects of KD on NLRP3 inflammasome and explore the potential molecular mechanisms. Methods : In in vivo study, mice were fed with KD for 3 weeks and then subjected to middle cerebral artery occlusion/reperfusion (MCAO/R)-injury. In in vitro study, SH-SY-5Y cells were treated with β-hydroxybutyrate (BHB) followed by oxygen-glucose deprivation/reoxygenation (OGD/R)...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29648974/traumatic-brain-injury-induced-acute-lung-injury-evidence-for-activation-and-inhibition-of-a-neural-respiratory-inflammasome-axis
#12
Nadine Kerr, Juan Pablo De Rivero Vaccari, Sam Abbassi, Harmanpreet Kaur, Ronald Zambrano, Shu Wu, W Dalton Dietrich, Robert W Keane
Approximately 20-25 percent of Traumatic Brain Injury subjects develop Acute Lung Injury (ALI), but the pathomechanisms of TBI-induced ALI remain poorly defined. Our previous work has shown that the inflammasome plays a critical role in TBI-induced secondary pathophysiology and that inflammasome proteins are released in Extracellular Vesicles (EV) after TBI. Here we investigated whether EV-mediated inflammasome signaling contributed to the etiology of TBI-induced ALI. C57/BL6 male mice were subjected to controlled cortical impact, and the brains and lungs were examined for inflammasome activation and ALI at 4 hours and 24 hours after TBI...
March 5, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29615953/inflammasome-proteins-as-biomarkers-of-multiple-sclerosis
#13
Robert W Keane, W Dalton Dietrich, Juan Pablo de Rivero Vaccari
Multiple sclerosis (MS) is an autoimmune disease that affects the brain and spinal cord. The inflammasome is a multiprotein complex that contributes to the innate immune response in animal models of MS as well as in patients with the disease. Important to the care of patients with MS is the need for biomarkers that can predict disease onset, disease exacerbation, as well as response to treatment. In this study, we analyzed serum samples from 32 patients with MS and 120 age-matched controls, and provide receiver operator characteristic (ROC) curves with associated confidence intervals following analyses of serum samples from patients with MS, most of which had the relapsing-remitting form of the disease, and from healthy unaffected donors, and determine the sensitivity and specificity of inflammasome proteins as biomarkers of MS...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29578616/tauroursodeoxycholic-acid-produces-antidepressant-like-effects-in-a-chronic-unpredictable-stress-model-of-depression-via-attenuation-of-neuroinflammation-oxido-nitrosative-stress-and-endoplasmic-reticulum-stress
#14
Xu Lu, Rong-Rong Yang, Jin-Lin Zhang, Peng Wang, Yu Gong, Wen-Feng Hu, Yue Wu, Min-Hui Gao, Chao Huang
Depression is a common psychiatric disorder with heavy economic and social burdens. Searching new agents with better antidepressant-like activities is of great significance for depression therapy. Tauroursodeoxycholic acid (TUDCA), a clinical drug for gallstone treatment, possesses neuroprotective effects in different brain disorders. However, whether it affects depression remains unclear. We addressed this issue by evaluating the effect of TUDCA on depression induced by chronic unpredictable stress (CUS). Results showed that TUDCA treatment at 200 but not 100 mg/kg prevented the 5 weeks of CUS-induced increases in the immobile time of C57BL6/J mice in the experiments of forced swimming test and tail suspension test as well as the CUS-induced decrease in sucrose intake and crossing numbers in the open-field test, and did not enhance the antidepressant-like effect of fluoxetine...
March 26, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29522854/chronic-amyloid-%C3%AE-oligomer-infusion-evokes-sustained-inflammation-and-microglial-changes-in-the-rat-hippocampus-via-nlrp3
#15
Csaba Fekete, Csaba Vastagh, Ádám Dénes, Erik Hrabovszky, Gábor Nyiri, Imre Kalló, Zsolt Liposits, Miklós Sárvári
Microglia are instrumental for recognition and elimination of amyloid β1-42 oligomers (AβOs), but the long-term consequences of AβO-induced inflammatory changes in the brain are unclear. Here, we explored microglial responses and transciptome-level inflammatory signatures in the rat hippocampus after chronic AβO challenge. Middle-aged Long Evans rats received intracerebroventricular infusion of AβO or vehicle for 4 weeks, followed by treatment with artificial CSF or MCC950 for the subsequent 4 weeks...
March 6, 2018: Neuroscience
https://www.readbyqxmd.com/read/29508284/nlrs-as-helpline-in-the-brain-mechanisms-and-therapeutic-implications
#16
REVIEW
Shalini Singh, Sushmita Jha
Nucleotide binding domain, leucine-rich repeat containing proteins (NLRs) are a family of pattern recognition receptors involved in major innate immune defense mechanisms. NLRs play a key role in several cancers, autoimmune, and inflammation-associated diseases. Association of NLRP3 has been widely investigated in neurodegenerative diseases, chronic alcoholism, depression, traumatic brain injury, and pathogenic infections. Several research studies have shown possible involvement of various other inflammasome-forming and non-inflammasome-forming NLRs in the brain; however, their mechanisms of action are yet to be defined clearly...
March 6, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29492520/-pyroptosis-and-stroke
#17
Biao Tang, Chang-Qing Deng
Pyroptosis is a form of inflammatory programmed cell death activated by caspase-1 and caspase-4/5/11, and involves in the pathogenesis of infectious diseases and nervous system diseases. Pyroptosis is mediated by canonical inflammasome pathway and non-canonical inflammasome pathway. The canonical inflammasome pathway is activated in stroke and aggravates brain injury. Inhibition of inflammasome, caspase-1, IL-1β and IL-18 ameliorates brain injury. These studies indicate that canonical inflammasome pathway contributes to post-stroke brain injury, therefore, pyroptosis has become a potential therapeutic target for preventing excessive cell death during stroke...
February 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/29488135/thioredoxin-interacting-protein-txnip-in-cerebrovascular-and-neurodegenerative-diseases-regulation-and-implication
#18
REVIEW
Sanaz Nasoohi, Saifudeen Ismael, Tauheed Ishrat
Neurological diseases, including acute attacks (e.g., ischemic stroke) and chronic neurodegenerative diseases (e.g., Alzheimer's disease), have always been one of the leading cause of morbidity and mortality worldwide. These debilitating diseases represent an enormous disease burden, not only in terms of health suffering but also in economic costs. Although the clinical presentations differ for these diseases, a growing body of evidence suggests that oxidative stress and inflammatory responses in brain tissue significantly contribute to their pathology...
February 27, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29477641/nlrp3-dependent-synaptic-plasticity-deficit-in-an-alzheimer-s-disease-amyloidosis-model-in-vivo
#19
Yingjie Qi, Igor Klyubin, A Claudio Cuello, Michael J Rowan
Pro-inflammatory mechanisms have recently emerged as an important component of early Alzheimer's disease (AD) pathogenesis. A particularly attractive therapeutic strategy is to selectively prevent the disruptive effects of activation of the innate immune system in the brain at an early transitional stage by reducing the production or directly neutralizing pro-inflammatory cytokines, in particular IL-1β and TNF-α. Here we tested their in vivo effects on synaptic plasticity deficits, which provide sensitive and robust measures of synaptic failure, in a rat model of AD amyloidosis...
June 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29449625/toll-like-receptor-4-modulation-influences-human-neural-stem-cell-proliferation-and-differentiation
#20
Chiara Grasselli, Daniela Ferrari, Cristina Zalfa, Matias Soncini, Gianluigi Mazzoccoli, Fabio A Facchini, Laura Marongiu, Francesca Granucci, Massimiliano Copetti, Angelo Luigi Vescovi, Francesco Peri, Lidia De Filippis
Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brain and cultured in vitro as neurospheres in compliance with Good Manifacture Procedures (GMP) guidelines. Similar batches have been used in recent clinical trials in ALS patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD-2 co-receptors, and TLR4 expression is downregulated upon differentiation...
February 15, 2018: Cell Death & Disease
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