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https://www.readbyqxmd.com/read/29049420/production-of-proinflammatory-mediators-in-activated-microglia-is-synergistically-regulated-by-notch-1-glycogen-synthase-kinase-gsk-3%C3%AE-and-nf-%C3%AE%C2%BAb-p65-signalling
#1
Qiong Cao, Aparna Karthikeyan, S Thameem Dheen, Charanjit Kaur, Eng-Ang Ling
Microglia activation and associated inflammatory response are involved in the pathogenesis of different neurodegenerative diseases. We have reported that Notch-1 and NF-κB/p65 signalling pathways operate in synergy in regulating the production of proinflammatory mediators in activated microglia. In the latter, there is also evidence by others that glycogen synthase kinase 3β (GSK-3β) mediates the release of proinflammatory cytokines but the interrelationships between the three signalling pathways have not been fully clarified...
2017: PloS One
https://www.readbyqxmd.com/read/29046475/evidence-for-mast-cells-contributing-to-neuromuscular-pathology-in-an-inherited-model-of-als
#2
Emiliano Trias, Sofía Ibarburu, Romina Barreto-Núñez, Valentina Varela, Ivan C Moura, Patrice Dubreuil, Olivier Hermine, Joseph S Beckman, Luis Barbeito
Evidence indicates that neuroinflammation contributes to motor neuron degeneration in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease leading to progressive muscular paralysis. However, it remains elusive whether inflammatory cells can interact with degenerating distal motor axons, influencing the progressive denervation of neuromuscular junctions (NMJs). By analyzing the muscle extensor digitorum longus (EDL) following paralysis onset in the SOD1G93A rat model, we have observed a massive infiltration and degranulation of mast cells, starting after paralysis onset and correlating with progressive NMJ denervation...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29043065/cns-cell-type-localization-and-lps-response-of-tlr-signaling-pathways
#3
Gizelle M McCarthy, Courtney R Bridges, Yuri A Blednov, R Adron Harris
Background: Innate immune signaling in the brain has emerged as a contributor to many central nervous system (CNS) pathologies, including mood disorders, neurodegenerative disorders, neurodevelopmental disorders, and addiction. Toll-like receptors (TLRs), a key component of the innate immune response, are particularly implicated in neuroimmune dysfunction. However, most of our understanding about TLR signaling comes from the peripheral immune response, and it is becoming clear that the CNS immune response is unique...
2017: F1000Research
https://www.readbyqxmd.com/read/29041969/glial-cells-are-functionally-impaired-in-juvenile-neuronal-ceroid-lipofuscinosis-and-detrimental-to-neurons
#4
Lotta Parviainen, Sybille Dihanich, Greg W Anderson, Andrew M Wong, Helen R Brooks, Rosella Abeti, Payam Rezaie, Giovanna Lalli, Simon Pope, Simon J Heales, Hannah M Mitchison, Brenda P Williams, Jonathan D Cooper
The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically occurs early in disease progression and predicts where neuron loss subsequently occurs. We have found that in the most common juvenile form of NCL (CLN3 disease or JNCL) this glial response is less pronounced in both mouse models and human autopsy material, with the morphological transformation of both astrocytes and microglia severely attenuated or delayed...
October 17, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29040306/micheliolide-suppresses-lps-induced-neuroinflammatory-responses
#5
Zhaomeng Sun, Guodong Li, Tanjun Tong, Jun Chen
Microglia-involved neuroinflammation is thought to promote brain damage in various neurodegenerative disorders. Thus, inhibition of microglial over-activation may have a therapeutic benefit for the treatment of neurodegenerative disorders. Micheliolide (MCL) is a sesquiterpene lactone which inhibits various inflammatory response. However, whether MCL can inhibit neuroinflammation caused by LPS-activated BV2 microglia has not yet been explored. In this study, we demonstrated that treatment of BV2 cells with MCL significantly repressed LPS-stimulated nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, as well as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) induction...
2017: PloS One
https://www.readbyqxmd.com/read/29038051/integrated-approach-reveals-diet-apoe-genotype-and-sex-affect-immune-response-in-app-mice
#6
Kyong Nyon Nam, Cody M Wolfe, Nicholas F Fitz, Florent Letronne, Emilie L Castranio, Anais Mounier, Jonathan Schug, Iliya Lefterov, Radosveta Koldamova
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that is influenced by genetic and environmental risk factors, such as inheritance of ε4 allele of APOE (APOE4), sex and diet. Here, we examined the effect of high fat diet (HFD) on amyloid pathology and expression profile in brains of AD model mice expressing human APOE isoforms (APP/E3 and APP/E4 mice). APP/E3 and APP/E4 mice were fed HFD or Normal diet for 3months. We found that HFD significantly increased amyloid plaques in male and female APP/E4, but not in APP/E3 mice...
October 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29036636/genetic-reduction-of-nrf2-exacerbates-cognitive-deficits-in-a-mouse-model-of-alzheimer-s-disease
#7
Caterina Branca, Eric Ferreira, Thuy-Vi Nguyen, Kristian Doyle, Antonella Caccamo, Salvatore Oddo
Aging is the major risk factor for several neurodegenerative diseases, including Alzheimer's disease (AD). However, the mechanisms by which aging contributes to neurodegeneration remain elusive. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor that regulates expression of a vast number of genes by binding to the antioxidant response element. Nrf2 levels decrease as a function of age, and reduced Nrf2 levels have been reported in postmortem human brains and animal models of AD...
September 19, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29034506/microglial-induced-m%C3%A3-ller-cell-gliosis-is-attenuated-by-progesterone-in-a-mouse-model-of-retinitis-pigmentosa
#8
Sarah L Roche, Ana M Ruiz-Lopez, Jennifer N Moloney, Ashleigh M Byrne, Thomas G Cotter
Norgestrel, a progesterone analogue, has demonstrated neuroprotective effects in a mouse model of retinitis pigmentosa. Neuroprotection is achieved in part through Norgestrels anti-inflammatory properties, alleviating detrimental microglial activity. Gliosis is a feature of many neurodegenerative diseases of the retina, including retinitis pigmentosa. Müller glia, a type of macroglia found in the retina, are major contributors of gliosis, characterized by the upregulation of glial fibrillary acidic protein (GFAP)...
October 16, 2017: Glia
https://www.readbyqxmd.com/read/29032655/microglial-involvement-in-the-development-of-olfactory-dysfunction
#9
REVIEW
Yoojin Seo, Hyung-Sik Kim, Kyung-Sun Kang
Olfaction is one of the oldest and important senses for life. Olfactory impairment is the most common clinical manifestation among elderly, and its prevalence is sharply increased with aging. Importantly, growing evidence has shown that olfactory dysfunction is the first sign of neurodegeneration, indicating the importance of olfactory assessment as an early diagnostic marker for the detection of neurological disorders. In this review, we described the nature of olfactory dysfunction and the advantage of animal models in olfaction study with brief introduction of olfactory behavior tests widely used in this field...
October 13, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/29027011/let-s-make-microglia-great-again-in-neurodegenerative-disorders
#10
REVIEW
Marie-Victoire Guillot-Sestier, Terrence Town
All of the common neurodegenerative disorders-Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and prion diseases-are characterized by accumulation of misfolded proteins that trigger activation of microglia; brain-resident mononuclear phagocytes. This chronic form of neuroinflammation is earmarked by increased release of myriad cytokines and chemokines in patient brains and biofluids. Microglial phagocytosis is compromised early in the disease process, obfuscating clearance of abnormal proteins...
October 12, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29024008/immunization-with-%C3%AE-synuclein-grp94-reshapes-peripheral-immunity-and-suppresses-microgliosis-in-a-chronic-parkinsonism-model
#11
Javier Villadiego, Adahir Labrador-Garrido, Jaime M Franco, Magdalena Leal-Lasarte, Erwin J De Genst, Christopher M Dobson, David Pozo, Juan J Toledo-Aral, Cintia Roodveldt
Neuroinflammation mediated by chronically activated microglia, largely caused by abnormal accumulation of misfolded α-synuclein (αSyn) protein, is known to contribute to the pathophysiology of Parkinson's disease (PD). In this work, based on the immunomodulatory activities displayed by particular heat-shock proteins (HSPs), we tested a novel vaccination strategy that used a combination of αSyn and Grp94 (HSPC4 or Gp96) chaperone and a murine PD model. We used two different procedures, first, the adoptive transfer of splenocytes from αSyn/Grp94-immunized mice to recipient animals, and second, direct immunization with αSyn/Grp94, to study the effects in a chronic mouse MPTP-model of parkinsonism...
October 11, 2017: Glia
https://www.readbyqxmd.com/read/29023416/neuro-coagulopathy-blood-coagulation-factors-in-central-nervous-system-diseases
#12
REVIEW
Ciro De Luca, Assunta Virtuoso, Nicola Maggio, Michele Papa
Blood coagulation factors and other proteins, with modulatory effects or modulated by the coagulation cascade have been reported to affect the pathophysiology of the central nervous system (CNS). The protease-activated receptors (PARs) pathway can be considered the central hub of this regulatory network, mainly through thrombin or activated protein C (aPC). These proteins, in fact, showed peculiar properties, being able to interfere with synaptic homeostasis other than coagulation itself. These specific functions modulate neuronal networks, acting both on resident (neurons, astrocytes, and microglia) as well as circulating immune system cells and the extracellular matrix...
October 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29020624/temporal-tracking-of-microglia-activation-in-neurodegeneration-at-single-cell-resolution
#13
Hansruedi Mathys, Chinnakkaruppan Adaikkan, Fan Gao, Jennie Z Young, Elodie Manet, Martin Hemberg, Philip L De Jager, Richard M Ransohoff, Aviv Regev, Li-Huei Tsai
Microglia, the tissue-resident macrophages in the brain, are damage sensors that react to nearly any perturbation, including neurodegenerative diseases such as Alzheimer's disease (AD). Here, using single-cell RNA sequencing, we determined the transcriptome of more than 1,600 individual microglia cells isolated from the hippocampus of a mouse model of severe neurodegeneration with AD-like phenotypes and of control mice at multiple time points during progression of neurodegeneration. In this neurodegeneration model, we discovered two molecularly distinct reactive microglia phenotypes that are typified by modules of co-regulated type I and type II interferon response genes, respectively...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28994715/%C3%AE-amyloid-and-the-pathomechanisms-of-alzheimer-s-disease-a-comprehensive-view
#14
REVIEW
Botond Penke, Ferenc Bogár, Lívia Fülöp
Protein dyshomeostasis is the common mechanism of neurodegenerative diseases such as Alzheimer's disease (AD). Aging is the key risk factor, as the capacity of the proteostasis network declines during aging. Different cellular stress conditions result in the up-regulation of the neurotrophic, neuroprotective amyloid precursor protein (APP). Enzymatic processing of APP may result in formation of toxic Aβ aggregates (β-amyloids). Protein folding is the basis of life and death. Intracellular Aβ affects the function of subcellular organelles by disturbing the endoplasmic reticulum-mitochondria cross-talk and causing severe Ca(2+)-dysregulation and lipid dyshomeostasis...
October 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28989002/chi3l1-and-chi3l2-overexpression-in-motor-cortex-and-spinal-cord-of-sals-patients
#15
C Sanfilippo, A Longo, F Lazzara, D Cambria, G Distefano, M Palumbo, A Cantarella, L Malaguarnera, M Di Rosa
BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the degeneration and death of upper (UMN) and lower (LMN) motor neurons. In the last decade, it has been shown that Chitinases are an important prognostic indicator of neuro-inflammatory damage induced by microglia and astrocytes. MATERIALS AND METHODS: We analyzed microarray datasets obtained from the Array Express in order to verify the expression levels of CHI3L1 and CHI3L2 in motor cortex biopsies of sALS patients with different survival times...
October 5, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28987033/trem2-expression-in-the-human-brain-a-marker-of-monocyte-recruitment
#16
Marie Fahrenhold, Sonja Rakic, John Classey, Carol Brayne, Paul G Ince, James A R Nicoll, Delphine Boche
Mutation in the triggering receptor expressed on myeloid cells (TREM) 2 gene has been identified as a risk factor for several neurodegenerative diseases including Alzheimer's disease (AD). Experimental studies using animal models of AD have highlighted a number of functions associated with TREM2 and its expression by microglial cells. It has therefore been assumed that this is also the case in humans. However, there is very limited information concerning the cellular expression of TREM2 in the human brain. As part of investigations of microglia using post-mortem resources provided by the Medical Research Council Cognitive Function and Ageing Studies (MRC-CFAS), we immunostained the cerebral cortex of 299 participants for TREM2 using the Sigma antibody HPA010917 and compared with the macrophage/microglial markers Iba1 and CD68...
October 7, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28985224/caspase-8-association-with-alzheimer-s-disease-and-functional-analysis-of-rare-variants
#17
Jan Rehker, Johanna Rodhe, Ryan R Nesbitt, Evan A Boyle, Beth K Martin, Jenny Lord, Ilker Karaca, Adam Naj, Frank Jessen, Seppo Helisalmi, Hilkka Soininen, Mikko Hiltunen, Alfredo Ramirez, Martin Scherer, Lindsay A Farrer, Jonathan L Haines, Margaret A Pericak-Vance, Wendy H Raskind, Carlos Cruchaga, Gerard D Schellenberg, Bertrand Joseph, Zoran Brkanac
The accumulation of amyloid beta (Aβ) peptide (Amyloid cascade hypothesis), an APP protein cleavage product, is a leading hypothesis in the etiology of Alzheimer's disease (AD). In order to identify additional AD risk genes, we performed targeted sequencing and rare variant burden association study for nine candidate genes involved in the amyloid metabolism in 1886 AD cases and 1700 controls. We identified a significant variant burden association for the gene encoding caspase-8, CASP8 (p = 8.6x10-5). For two CASP8 variants, p...
2017: PloS One
https://www.readbyqxmd.com/read/28984087/effects-of-rhei-undulati-rhizoma-on-lipopolysaccharide-induced-neuroinflammation-in-vitro-and-in-vivo
#18
Deok-Sang Hwang, Pil Sung Gu, Namkwon Kim, Young Pyo Jang, Myung Sook Oh
Neuroinflammation plays a critical role in the pathogenesis of degenerative brain diseases such as Alzheimer's disease and Parkinson's disease. Microglia are the major components of the brain immune system that regulate inflammatory processes. Activated microglia release pro-inflammatory factors and cytokines, resulting in neuronal cell death. We focused on inhibiting the activation of microglia from a stimulus as a strategy to search for neuroprotective drugs. Rhei Undulati Rhizoma (RUR) is traditionally used to treat various inflammatory disorders...
October 6, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28983846/microglial-activation-results-in-inhibition-of-tgf-%C3%AE-regulated-gene-expression
#19
Kwame Ofori Affram, Kendall Mitchell, Aviva J Symes
Chronic inflammation mediated by persistent microglial activation is associated with the pathogenesis of neurodegenerative diseases. The mechanisms underlying chronic microglial activation are poorly understood. We have previously shown that anti-inflammatory TGF-β signaling is inhibited in LPS-treated microglia. In this study, we assessed whether different disease-related microglial activators could downregulate TGF-β induction of gene expression. We examined the effects of amyloid β (Aβ) (1-42)- or heat-killed Listeria monocytogenes (HKLM) on the TGF-β-regulated gene expression in primary rat microglia...
October 5, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28982340/the-18-kda-translocator-protein-tspo-as-a-cns-drug-target-finding-our-way-through-the-neuroinflammation-fog
#20
Michaela D Filiou, Richard B Rabati, Manuel B Graeber
The 18-kDa translocator protein (TSPO) is located in the outer mitochondrial membrane where it is thought to co-regulate steroidogenesis, cellular bioenergetics as well as several other cellular processes. Originally discovered as a binding site for diazepam outside the CNS, notably in steroidogenic tissue and mononuclear phagocytes, the TSPO's historical designation was peripheral benzodiazepine receptor. Much of the recent interest in the TSPO is due to the observation that its regulation in the brain is associated with microglial activation...
October 4, 2017: CNS & Neurological Disorders Drug Targets
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