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Inflammasome neurodegeneration

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https://www.readbyqxmd.com/read/28912345/a-novel-bibenzyl-compound-20c-protected-mice-from-mptp-p-toxicity-by-regulating-alpha-synuclein-related-inflammatory-response
#1
Qiu-Shuang Zhang, Yang Heng, Ying Chen, Piao Luo, Lu Wen, Zhao Zhang, Yu-He Yuan, Nai-Hong Chen
The novel bibenzyl compound 20C plays a neuroprotective role in vitro, but its effects in vivo have not been elucidated. In this study, we estimated the efficacy of 20C in vivo using a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p) mouse model from behavior, dopamine and neuron, and then the possible mechanisms for these effects were further investigated. The experimental results showed that 20C improved behavioral deficits, attenuated dopamine depletion, reduced dopaminergic neuron loss, protected blood brain barrier structure, ameliorated α-synuclein dysfunction, suppressed glial activation, and regulated both NF-κB signaling and the NLRP3 inflammasome pathway...
September 14, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28866823/neuroprotective-effects-of-baicalein-on-acrolein-induced-neurotoxicity-in-the-nigrostriatal-dopaminergic-system-of-rat-brain
#2
Wei-Zhong Zhao, Hsiang-Tsui Wang, Hui-Ju Huang, Yu-Li Lo, Anya Maan-Yuh Lin
Elevated levels of acrolein, an α,β-unsaturated aldehyde are detected in the brain of patients with Parkinson's disease (PD). In the present study, the neuroprotective effect of baicalein (a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi) on acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was investigated using local infusion of acrolein in the substantia nigra (SN) of rat brain. Systemic administration of baicalein (30 mg/kg, i.p.) significantly attenuated acrolein-induced elevations in 4-hydroxy-2-noneal (a product of lipid peroxidation), N-(3-formyl-3,4-dehydropiperidino)lysine (a biomarker of acrolein-conjugated proteins), and heme-oxygenase-1 levels (a redox-regulated protein) in the infused SN, indicating that baicalein inhibited acrolein-induced oxidative stress and protein conjugation...
September 2, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28732502/chronic-glucocorticoid-exposure-activates-bk-nlrp1-signal-involving-in-hippocampal-neuron-damage
#3
Biqiong Zhang, Yaodong Zhang, Wenning Wu, Tanzhen Xu, Yanyan Yin, Junyan Zhang, Dake Huang, Weizu Li
BACKGROUND: Neuroinflammation mediated by NLRP1 (nucleotide-binding oligomerization domain (NOD)-like receptor protein 1) inflammasome plays an important role in many neurological diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). Our previous studies showed that chronic glucocorticoid (GC) exposure increased brain inflammation via NLRP1 inflammasome and induce neurodegeneration. However, little is known about the mechanism of chronic GC exposure on NLRP1 inflammasome activation in hippocampal neurons...
July 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28605710/chronic-dexamethasone-treatment-results-in-hippocampal-neurons-injury-due-to-activate-nlrp1-inflammasome-in-vitro
#4
Biqiong Zhang, Yaodong Zhang, Tanzhen Xu, Yanyan Yin, Rongrong Huang, Yuchan Wang, Junyan Zhang, Dake Huang, Weizu Li
Neuroinflammation mediated by NLRP-1 inflammasome plays an important role in the pathogenesis of neurodegeneration diseases such as Alzheimer's disease (AD). Chronic glucocorticoids (GCs) exposure has deleterious effect on the structure and function of neurons and was found to be correlated with development and progression of AD. We hypothesize that chronic glucocorticoids may down-regulate the expression of glucocorticoids receptor (GR) and activate NLRP-1 inflammasome in hippocampal neurons, which may promote neuroinflammation and induce neuronal injury...
June 9, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28413194/dual-role-of-cellular-prion-protein-in-normal-host-and-alzheimer-s-disease
#5
REVIEW
Takashi Onodera
Using PrP(C)-knockout cell lines, it has been shown that the inhibition of apoptosis through STI1 is mediated by PrP(C)-dependent SOD activation. Antioxidant PrP(C) may contribute to suppression of inflammasome activation. PrP(C) is functionally involved in copper metabolism, signal transduction, neuroprotection, and cell maturation. Recently several reports have shown that PrP(C) participates in trans-membrane signaling processes associated with hematopoietic stem cell replication and neuronal differentiation...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28404595/nlr-members-nlrc4-and-nlrp3-mediate-sterile-inflammasome-activation-in-microglia-and-astrocytes
#6
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...
May 1, 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
#7
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/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#8
Elena Fetisova, Boris Chernyak, Galina Korshunova, Maria Muntyan, Vladimir 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...
2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28186177/the-far-reaching-scope-of-neuroinflammation-after-traumatic-brain-injury
#9
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/27997058/inflammasome-activation-in-multiple-sclerosis-and-experimental-autoimmune-encephalomyelitis-eae
#10
William Barclay, Mari L Shinohara
The aptly named inflammasomes are powerful signaling complexes that sense inflammatory signals under a myriad of conditions, including those from infections and endogenous sources. The inflammasomes promote inflammation by maturation and release of the pro-inflammatory cytokines, IL-1β and IL-18. Several inflammasomes have been identified so far, but this review focuses mainly on the NLRP3 inflammasome. By still ill-defined activation mechanisms, a sensor molecule, NLRP3 (NACHT, LRR and PYD domains-containing protein 3), responds to danger signals and rapidly recruits ASC (apoptosis-associated speck-like protein containing a CARD) and pro-caspase-1 to form a large oligomeric signaling platform-the inflammasome...
March 2017: Brain Pathology
https://www.readbyqxmd.com/read/27880990/neurodegeneration-and-nlrp3-inflammasome-expression-in-the-anterior-thalamus-of-sod1-g93a-als-mice
#11
Berthold Debye, Lena Schmülling, Lepu Zhou, Gabriele Rune, Cordian Beyer, Sonja Johann
Nowadays, Amyotrophic lateral sclerosis (ALS) is considered as a multisystem disorder, characterized by a primary degeneration of motor neurons as well as neuropathological changes in non-motor regions. Neurodegeneration in subcortical areas, such as the thalamus, are believed to contribute to cognitive and behavioural abnormalities in ALS patients. In the present study, we investigated neurodegenerative changes including neuronal loss and glia pathology in the anterodorsal thalamic nucleus (AD) of SOD1(G93A) mice, a widely used animal model for ALS...
November 23, 2016: Brain Pathology
https://www.readbyqxmd.com/read/27862176/inflammasomes-hormesis-and-antioxidants-in-neuroinflammation-role-of-nrlp3-in-alzheimer-disease
#12
REVIEW
Manuela Pennisi, Rosalia Crupi, Rosanna Di Paola, Maria Laura Ontario, Rita Bella, Edward J Calabrese, Roberto Crea, Salvatore Cuzzocrea, Vittorio Calabrese
Alzheimer disease (AD) is a progressive neurodegenerative disorder leading to cognitive decline, neuropsychiatric symptoms, disability, caregiver burden, and premature death. It represents the most prevalent cause of dementia, and its incidence rates exponentially increase with increasing age. The number of Americans living with AD is rapidly increasing. An estimated 5.4 million Americans of all ages have AD in 2016. One in nine people aged 65 and older has AD, and by midcentury, someone in the United States will develop the disease every 33 sec...
November 8, 2016: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27718173/neuroinflammation-immune-system-and-alzheimer-disease-searching-for-the-missing-link
#13
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/27600432/mitochondria-and-the-nlrp3-inflammasome-physiological-and-pathological-relevance
#14
REVIEW
Je-Wook Yu, Myung-Shik Lee
The NLRP3 inflammasome is assembled and activated in certain types of myeloid cells upon sensing microbe-derived toxins or host-derived danger signals. Activation of the NLRP3 inflammasome by endogenous ligands has been discovered in various disorders, including metabolic syndrome, type 2 diabetes, atherosclerosis, gout, reperfusion injury of the heart, neurodegeneration, such as Alzheimer's disease, chronic kidney diseases, and macular degeneration of the eyes. Despite the potential significance of the NLRP3 inflammasome in the pathogenesis of several diseases, details on the activation mechanism of the NLRP3 inflammasome by a variety of stimulators have yet to be reported...
November 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27533933/caspase-1-inhibition-attenuates-activation-of-bv2-microglia-induced-by-lps-treated-raw264-7-macrophages
#15
Yang Pan, Bo Shen, Qin Gao, Jun Zhu, Jingde Dong, Li Zhang, Yingdong Zhang
Neuroinflammation has been recognized as a factor in the pathogenesis of neurodegenerative diseases. Emerging evidence suggests that peripheral inflammation, besides neuroinflammation, functions as a modulator of disease progression and neuropathology in several neurodegenerative diseases. However, detailed correlations among peripheral inflammation, neuroinflammation and neurodegeneration remain unknown. In the present study, we prepared a peripheral inflammation model with lipopolysaccharides (LPS)-stimulated RAW264...
May 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27486046/inflammasomes-link-vascular-disease-with-neuroinflammation-and-brain-disorders
#16
REVIEW
Nikolett Lénárt, David Brough, Ádám Dénes
The role of inflammation in neurological disorders is increasingly recognised. Inflammatory processes are associated with the aetiology and clinical progression of migraine, psychiatric conditions, epilepsy, cerebrovascular diseases, dementia and neurodegeneration, such as seen in Alzheimer's or Parkinson's disease. Both central and systemic inflammatory actions have been linked with the development of brain diseases, suggesting that complex neuro-immune interactions could contribute to pathological changes in the brain across multiple temporal and spatial scales...
October 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27251615/transient-p2x7-receptor-antagonism-produces-lasting-reductions-in-spontaneous-seizures-and-gliosis-in-experimental-temporal-lobe-epilepsy
#17
Alba Jimenez-Pacheco, Miguel Diaz-Hernandez, Marina Arribas-Blázquez, Amaya Sanz-Rodriguez, Luis A Olivos-Oré, Antonio R Artalejo, Mariana Alves, Michael Letavic, M Teresa Miras-Portugal, Ronan M Conroy, Norman Delanty, Michael A Farrell, Donncha F O'Brien, Anindya Bhattacharya, Tobias Engel, David C Henshall
UNLABELLED: Neuroinflammation is thought to contribute to the pathogenesis and maintenance of temporal lobe epilepsy, but the underlying cell and molecular mechanisms are not fully understood. The P2X7 receptor is an ionotropic receptor predominantly expressed on the surface of microglia, although neuronal expression has also been reported. The receptor is activated by the release of ATP from intracellular sources that occurs during neurodegeneration, leading to microglial activation and inflammasome-mediated interleukin 1β release that contributes to neuroinflammation...
June 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27090302/inflammasome-signaling-affects-anxiety-and-depressive-like-behavior-and-gut-microbiome-composition
#18
M-L Wong, A Inserra, M D Lewis, C A Mastronardi, L Leong, J Choo, S Kentish, P Xie, M Morrison, S L Wesselingh, G B Rogers, J Licinio
The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1β and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress...
June 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/26978350/geranylgeraniol-and-neurological-impairment-involvement-of-apoptosis-and-mitochondrial-morphology
#19
Annalisa Marcuzzi, Elisa Piscianz, Marina Zweyer, Roberta Bortul, Claudia Loganes, Martina Girardelli, Gabriele Baj, Lorenzo Monasta, Claudio Celeghini
Deregulation of the cholesterol pathway is an anomaly observed in human diseases, many of which have in common neurological involvement and unknown pathogenesis. In this study we have used Mevalonate Kinase Deficiency (MKD) as a disease-model in order to investigate the link between the deregulation of the mevalonate pathway and the consequent neurodegeneration. The blocking of the mevalonate pathway in a neuronal cell line (Daoy), using statins or mevalonate, induced an increase in the expression of the inflammasome gene (NLRP3) and programmed cell death related to mitochondrial dysfunction...
March 11, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/26434621/chronic-glucocorticoids-exposure-enhances-neurodegeneration-in-the-frontal-cortex-and-hippocampus-via-nlrp-1-inflammasome-activation-in-male-mice
#20
Wen Hu, Yaodong Zhang, Wenning Wu, Yanyan Yin, Dake Huang, Yuchan Wang, Weiping Li, Weizu Li
Neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD) and depression. Chronic glucocorticoids (GCs) exposure has deleterious effects on the structure and function of neurons and is associated with development and progression of AD. However, little is known about the proinflammatory effects of chronic GCs exposure on neurodegeneration in brain. Therefore, the aim of this study was to evaluate the effects of chronic dexamethasone (DEX) treatment (5mg/kg, s...
February 2016: Brain, Behavior, and Immunity
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