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https://www.readbyqxmd.com/read/28427559/stress-induced-nlrp3-inflammasome-in-human-diseases
#1
Elísabet Alcocer-Gómez, Beatriz Castejón-Vega, Mario D Cordero
Stress is a complex event that induces disturbances to physiological and psychological homeostasis, and it may have a detrimental impact on certain brain and physiological functions. In the last years, a dual role of the stress effect has been studied in order to elucidate the molecular mechanism by which can induce physiological symptoms after psychological stress exposition and vice versa. In this sense, inflammation has been proposed as an important starring. And in the same line, the inflammasome complex has emerged to give responses because of its role of stress sensor...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28414101/autophagy-in-hemorrhagic-stroke-mechanisms-and-clinical-implications
#2
REVIEW
Haiying Li, Jiang Wu, Haitao Shen, Xiyang Yao, Chenglin Liu, S Pianta, J Han, C V Borlongan, Gang Chen
Accumulating evidence advances the critical role of autophagy in brain pathology after stroke. Investigations employing autophagy induction or inhibition using pharmacological tools or autophagy-related gene knockout mice have recently revealed the biological significance of intact and functional autophagy in stroke. Most of the reported cases attest to a pro-survival role for autophagy in stroke, by facilitating removal of damaged proteins and organelles, which can be recycled for energy generation and cellular defenses...
April 13, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28404595/nlr-members-nlrc4-and-nlrp3-mediate-sterile-inflammasome-activation-in-microglia-and-astrocytes
#3
Leslie Freeman, Haitao Guo, Clément N David, W June Brickey, Sushmita Jha, Jenny P-Y Ting
Inflammation in the brain accompanies several high-impact neurological diseases including multiple sclerosis (MS), stroke, and Alzheimer's disease. Neuroinflammation is sterile, as damage-associated molecular patterns rather than microbial pathogens elicit the response. The inflammasome, which leads to caspase-1 activation, is implicated in neuroinflammation. In this study, we reveal that lysophosphatidylcholine (LPC), a molecule associated with neurodegeneration and demyelination, elicits NLRP3 and NLRC4 inflammasome activation in microglia and astrocytes, which are central players in neuroinflammation...
April 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28401906/acrolein-acts-as-a-neurotoxin-in-the-nigrostriatal-dopaminergic-system-of-rat-involvement-of-%C3%AE-synuclein-aggregation-and-programmed-cell-death
#4
Yi-Ting Wang, Hui-Ching Lin, Wei-Zhong Zhao, Hui-Ju Huang, Yu-Li Lo, Hsiang-Tsui Wang, Anya Maan-Yuh Lin
Clinical studies report significant increases in acrolein (an α,β-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson's disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150 nmoles/0.5 μl) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) levels, dopamine transporter levels and TH-positive neurons in the infused SN as well as in striatal dopamine content...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28401330/cordycepin-confers-neuroprotection-in-mice-models-of-intracerebral-hemorrhage-via-suppressing-nlrp3-inflammasome-activation
#5
Yijun Cheng, Yongxu Wei, Wenlei Yang, Yaying Song, Hanbing Shang, Yu Cai, Zhebao Wu, Weiguo Zhao
Neuroinflammation has been recognized as a major contributor to brain injury caused by intracerebral hemorrhage (ICH). Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome acts as an important mediator of inflammatory response in various inflammation-related diseases including hemorrhagic insults. Cordycepin has recently been shown to possess anti-inflammatory effect; however, its role and the possible underlying mechanisms in ICH remain unclear. This study was designed to investigate the neuroprotective effect of cordycepin in mice models of ICH and to elucidate the underlying molecular mechanisms...
April 11, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28397070/ketone-bodies-as-anti-seizure-agents
#6
Timothy A Simeone, Kristina A Simeone, Jong M Rho
There is growing evidence that ketone bodies (KB)-derived from fatty acid oxidation and produced during fasting or consumption of high-fat diets-can exert broad neuroprotective effects. With respect to epilepsy, KB (such as β-hydroxybutyrate or BHB, acetoacetate and acetone) have been shown to block acutely induced and spontaneous recurrent seizures in various animal models. Although the mechanisms underlying the anti-seizure effects of KB have not been fully elucidated, recent experimental studies have invoked ketone-mediated effects on both inhibitory (e...
April 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28337127/nlrp3-inflammasome-in-neurological-diseases-from-functions-to-therapies
#7
REVIEW
Limin Song, Lei Pei, Shanglong Yao, Yan Wu, You Shang
Neuroinflammation has been identified as a causative factor of multiple neurological diseases. The nucleotide-binding oligomerization domain-, leucine-rich repeat- and pyrin domain-containing 3 (NLRP3) inflammasome, a subcellular multiprotein complex that is abundantly expressed in the central nervous system (CNS), can sense and be activated by a wide range of exogenous and endogenous stimuli such as microbes, aggregated and misfolded proteins, and adenosine triphosphate, which results in activation of caspase-1...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28331244/a-novel-role-for-brain-natriuretic-peptide-inhibition-of-il-1%C3%AE-secretion-via-downregulation-of-nf-kb-erk-1-2-and-nalp3-asc-caspase-1-activation-in-human-thp-1-monocyte
#8
Letizia Mezzasoma, Cinzia Antognelli, Vincenzo Nicola Talesa
Interleukin-1β (IL-1β) is a pleiotropic cytokine and a crucial mediator of inflammatory and immune responses. IL-1β processing and release are tightly controlled by complex pathways such as NF-kB/ERK1/2, to produce pro-IL-1β, and NALP3/ASC/Caspase-1 inflammasome, to produce the active secreted protein. Dysregulation of both IL-1β and its related pathways is involved in inflammatory/autoimmune disorders and in a wide range of other diseases. Identifying molecules modulating their expression is a crucial need to develop new therapeutic agents...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28326544/personalized-genetics-of-the-cholinergic-blockade-of-neuroinflammation
#9
REVIEW
Alon Simchovitz, Michael T Heneka, Hermona Soreq
Acetylcholine signaling is essential for cognitive functioning and blocks inflammation. To maintain homeostasis, cholinergic signaling is subjected to multi-leveled and bidirectional regulation by both proteins and non-coding microRNAs ('CholinomiRs'). CholinomiRs coordinate the cognitive and inflammatory aspects of cholinergic signaling by targeting major cholinergic transcripts including the acetylcholine hydrolyzing enzyme acetylcholinesterase (AChE). Notably, AChE inhibitors are the only currently approved line of treatment for Alzheimer's disease patients...
March 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#10
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/28300164/role-of-purinergic-signaling-in-experimental-pneumococcal-meningitis
#11
Marco Zierhut, Susanne Dyckhoff, Ilias Masouris, Matthias Klein, Sven Hammerschmidt, Hans-Walter Pfister, Korcan Ayata, Marco Idzko, Uwe Koedel
Excessive neutrophilic inflammation contributes to brain pathology and adverse outcome in pneumococcal meningitis (PM). Recently, we identified the NLRP3 inflammasome/interleukin (IL)-1β pathway as a key driver of inflammation in PM. A critical membrane receptor for NLRP3 inflammasome activation is the ATP-activated P2 purinoceptor (P2R) P2X7. Thus, we hypothesized involvement of ATP and P2Rs in PM. The functional role of ATP was investigated in a mouse meningitis model using P2R antagonists. Brain expression of P2Rs was assessed by RT-PCR...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28274860/purinergic-2x7-receptor-nlrp3-pathway-triggers-neuronal-apoptosis-after-ischemic-stroke-in-the-mouse
#12
Xinchun Ye, Tong Shen, Jinxia Hu, Liang Zhang, Yunshan Zhang, Lei Bao, Chengcheng Cui, Guoliang Jin, Kun Zan, Zuohui Zhang, Xinxin Yang, Hongjuan Shi, Jie Zu, Ming Yu, Chengjie Song, Yulan Wang, Suhua Qi, Guiyun Cui
Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950)...
March 6, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28270571/hiv-1-tat-primes-and-activates-microglial-nlrp3-inflammasome-mediated-neuroinflammation
#13
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. NLR family pyrin domain containing 3 (NLRP3) inflammasome has been implicated in HIV-induced microglial activation, but the mechanism(s) remain unclear. Because HIV-1 Transactivator of Transcription (Tat) protein 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...
March 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28263786/nlrp3-inflammasome-driven-pathways-in-depression-clinical-and-preclinical-findings
#14
REVIEW
Fernanda N Kaufmann, Ana Paula Costa, Gabriele Ghisleni, Alexandre P Diaz, Ana Lúcia S Rodrigues, Hugo Peluffo, Manuella P Kaster
Over the past three decades, an intricate interaction between immune activation, release of pro-inflammatory cytokines and changes in brain circuits related to mood and behavior has been described. Despite extensive efforts, questions regarding when inflammation becomes detrimental or how we can target the immune system to develop new therapeutic strategies for the treatment of psychiatric disorders remain unresolved. In this context, novel aspects of the neuroinflammatory process activated in response to stressful challenges have recently been documented in major depressive disorder (MDD)...
March 2, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28255908/nlrp3-inflammasome-inhibitor-ameliorates-amyloid-pathology-in-a-mouse-model-of-alzheimer-s-disease
#15
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/28238167/effects-of-cox1-2-5-lox-blockade-in-alzheimer-transgenic-3xtg-ad-mice
#16
Alessandra Bitto, Daniela Giuliani, Giovanni Pallio, Natasha Irrera, Eleonora Vandini, Fabrizio Canalini, Davide Zaffe, Alessandra Ottani, Letteria Minutoli, Mariagrazia Rinaldi, Salvatore Guarini, Francesco Squadrito, Domenica Altavilla
OBJECTIVE AND DESIGN: Alzheimer's disease (AD) is associated with amyloid plaques (Aβ) and hyperphosphorylated tau protein tangles in the brain. We investigated the possible neuroprotective role of flavocoxid, a dual inhibitor of cyclooxygenases-1/2 (COX-1/2) and 5-Lipoxygenase (5-LOX), in triple-transgenic (3xTg-AD) mice. SUBJECTS: Mice were 3 months at the beginning of the study. TREATMENT: Animals received once daily for 3-month saline solution or flavocoxid (20 mg/kg/ip)...
February 25, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28202418/ros-txnip-pathway-contributes-to-thrombin-induced-nlrp3-inflammasome-activation-and-cell-apoptosis-in-microglia
#17
Xinchun Ye, Dandan Zuo, Lu Yu, Liang Zhang, Jiao Tang, Chengcheng Cui, Lei Bao, Kun Zan, Zuohui Zhang, Xinxin Yang, Hao Chen, Hai Tang, Jie Zu, Hongjuan Shi, Guiyun Cui
There is no effective therapy for intracerebral hemorrhage (ICH) because of poor understanding of the mechanisms of brain injury after hemorrhage. The NLRP3 inflammasome, as a vital component of innate immune system, which is associated with a wide range of human CNS disorders, including ICH. But its detailed mechanisms in ICH remain mainly unclear. In this study, BV2 cells with thrombin exposure were used to investigate the role of NLRP3 inflammasome in thrombin-induced brain injury. We used western blot to detect NLRP3 inflammasome activation and the expression of thioredoxin binding protein (TXNIP), DCFH-DA to investigate intracellular reactive oxygen species (ROS), flow cytometry to analyze apoptosis...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28186177/the-far-reaching-scope-of-neuroinflammation-after-traumatic-brain-injury
#18
REVIEW
Dennis W Simon, Mandy J McGeachy, Hülya Bayır, Robert S B Clark, David J Loane, Patrick M Kochanek
The 'silent epidemic' of traumatic brain injury (TBI) has been placed in the spotlight as a result of clinical investigations and popular press coverage of athletes and veterans with single or repetitive head injuries. Neuroinflammation can cause acute secondary injury after TBI, and has been linked to chronic neurodegenerative diseases; however, anti-inflammatory agents have failed to improve TBI outcomes in clinical trials. In this Review, we therefore propose a new framework of targeted immunomodulation after TBI for future exploration...
March 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28181102/cerebrospinal-fluid-nlrp3-is-increased-after-severe-traumatic-brain-injury-in-infants-and-children
#19
Jessica S Wallisch, Dennis W Simon, Hülya Bayır, Michael J Bell, Patrick M Kochanek, Robert S B Clark
BACKGROUND: Inflammasome-mediated neuroinflammation may cause secondary injury following traumatic brain injury (TBI) in children. The pattern recognition receptors NACHT domain-, Leucine-rich repeat-, and PYD-containing Protein 1 (NLRP1) and NLRP3 are essential components of their respective inflammasome complexes. We sought to investigate whether NLRP1 and/or NLRP3 abundance is altered in children with severe TBI. METHODS: Cerebrospinal fluid (CSF) from children (n = 34) with severe TBI (Glasgow coma scale score [GCS] ≤8) who had externalized ventricular drains (EVD) placed for routine care was evaluated for NLRP1 and NLRP3 at 0-24, 25-48, 49-72, and >72 h post-TBI and was compared to infection-free controls that underwent lumbar puncture to rule out CNS infection (n = 8)...
February 8, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28178176/nlrp12-inflammasome-expression-in-the-rat-brain-in-response-to-lps-during-morphine-tolerance
#20
Sulie L Chang, Wenfei Huang, Xin Mao, Sabroni Sarkar
Morphine, an effective but addictive analgesic, can profoundly affect the inflammatory response to pathogens, and long-term use can result in morphine tolerance. Inflammasomes are protein complexes involved in the inflammatory response. The nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing (NLRP) 12 (NLRP12) inflammasome has been reported to have anti-inflammatory activity. In this study, we examined the expression of NLRP12 inflammasome related genes in the adult F344 rat brain in response to the bacterial endotoxin lipopolysaccharide (LPS) in the presence and absence of morphine tolerance...
February 6, 2017: Brain Sciences
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