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https://www.readbyqxmd.com/read/28930663/the-trem2-apoe-pathway-drives-the-transcriptional-phenotype-of-dysfunctional-microglia-in-neurodegenerative-diseases
#1
Susanne Krasemann, Charlotte Madore, Ron Cialic, Caroline Baufeld, Narghes Calcagno, Rachid El Fatimy, Lien Beckers, Elaine O'Loughlin, Yang Xu, Zain Fanek, David J Greco, Scott T Smith, George Tweet, Zachary Humulock, Tobias Zrzavy, Patricia Conde-Sanroman, Mar Gacias, Zhiping Weng, Hao Chen, Emily Tjon, Fargol Mazaheri, Kristin Hartmann, Asaf Madi, Jason D Ulrich, Markus Glatzel, Anna Worthmann, Joerg Heeren, Bogdan Budnik, Cynthia Lemere, Tsuneya Ikezu, Frank L Heppner, Vladimir Litvak, David M Holtzman, Hans Lassmann, Howard L Weiner, Jordi Ochando, Christian Haass, Oleg Butovsky
Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic β-amyloid (Aβ)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930607/transcriptomics-in-amyotrophic-lateral-sclerosis
#2
Marios G Krokidis, Panagiotis Vlamos
Amyotrophic lateral sclerosis (ALS) is an adult-onset, incurable neurodegenerative disease characterized by the selective death of upper and lowers motor neurons in the spinal cord, brainstem and motor cortex, which ultimately leads to paralysis and death within 2-3 years of onset. ALS is poorly understood, although multiple studies have been proposed to explain the pathophysiological mechanisms of the disorder. The development of microarray technology, for simultaneous analysis of the transcriptional expression of thousands of genes, has provided new possibilities to get better insights into the pathogenesis of ALS, and most important, potential new candidate targets for novel treatments...
January 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28930429/mapping-protein-targets-of-bioactive-small-molecules-using-lipid-based-chemical-proteomics
#3
Kenneth M Lum, Yoshiaki Sato, Brittney A Beyer, Warren C Plaisted, Justin L Anglin, Luke L Lairson, Benjamin F Cravatt
Lipids play critical roles in cell biology, often through direct interactions with proteins. We recently described the use of photoreactive lipid probes combined with quantitative mass spectrometry to globally map lipid-protein interactions, and the effects of drugs on these interactions, in cells. Here, we investigate the broader potential of lipid-based chemical proteomic probes for determining the cellular targets of biologically active small molecules, including natural product derivatives and repurposed drugs of ill-defined mechanisms...
September 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28929835/dab389il-2-recombinant-fusion-toxin-effect-on-lymphocyte-and-macrophage-producing-cytokine-subpopulation-cells-in-experimentally-induced-demyelinating-disease-in-mice
#4
Mahendra K Bhopale, Brendan Hilliard, Cris S Constantinescu, S Michael Phillips, Abdolmohamad Rostami
CONTEXT: We have reported previously that DAB389IL-2 recombinant fusion toxin targets IL-2R bearing CD4(+) cells, and suppresses demyelinating disease in acute (A) - and chronic (C) - experimental autoimmune encephalomyelitis (EAE) animal models of multiple sclerosis. OBJECTIVES: The present study was undertaken to investigate the effect of DAB389IL-2 treatment on various cytokine-secreting cell populations in A-EAE and C-EAE mice. MATERIALS AND METHODS: The effects of DAB389IL-2 at doses of 200-, 800-, or 1600 kU administered i...
September 20, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28929802/a-study-of-outcomes-of-patients-treated-at-a-uk-major-trauma-centre-for-moderate-or-severe-injuries-one-to-three-years-after-injury
#5
Stephen Spreadborough, Kate Radford, Roshan das Nair, Adam Brooks, Miriam Duffy
OBJECTIVE: To assess return to work outcomes of major trauma patients treated at a level 1 UK major trauma centre and evaluate factors associated with improved outcomes. DESIGN: Cross-sectional cohort design. SUBJECTS: In total, 99 patients at one, two or three years post-discharge from a Major Trauma Centre with an injury severity score above 9, in full-time work or education prior to injury, aged 18-70 and discharged between April 2012 and June 2015...
September 1, 2017: Clinical Rehabilitation
https://www.readbyqxmd.com/read/28929471/-delta-9-tetrahydrocannabinol-cannabidiol-in-the-treatment-of-spasticity-in-chronic-spinal-cord-injury-a-clinical-experience
#6
C Grao-Castellote, F Torralba-Collados, L M Gonzalez, M Giner-Pascual
INTRODUCTION: Spasticity in chronic spinal cord injury is a condition that can have negative repercussions on the patient's quality of life. Its treatment is complex and sometimes the outcome is insufficient. Cannabinoids have recently been used in multiple sclerosis to successfully treat spasticity that is refractory to other therapies. AIM: To quantify the clinical response of a group of patients with spastic chronic spinal cord injury to the orally administered drug delta-9-tetrahydrocannabinol-cannabidiol (Sativex ®) as medication for use in special situations...
October 1, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28929408/yokukansan-reduces-cuprizone-induced-demyelination-in-the-corpus-callosum-through-anti-inflammatory-effects-on-microglia
#7
Taichi Nomura, Yoshio Bando, Hua You, Tatsuhide Tanaka, Shigetaka Yoshida
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). The release of inflammatory cytokines and pro-oxidant molecules from microglia has been shown to play a key role in the pathology of MS. Thus, suppression of microglial cell activation is an attractive therapeutic option. Yokukansan, a traditional Japanese herbal medicine, has been shown to suppress microglial activity in the CNS. However, whether or not yokukansan reduces demyelination observed in the CNS during MS remains unknown...
September 19, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28928949/plasmapheresis-in-neurological-disorders-six-years-experience-from-university-clinical-center-tuzla
#8
Osman Sinanović, Sanela Zukić, Adnan Burina, Nermina Pirić, Renata Hodžić, Mirza Atić, Mirna Alečković-Halilović, Enisa Mešić
BACKGROUND: Therapeutic plasma exchange (TPE) is an extracorporeal blood purification technique that is designed to remove substances with a large molecular weight. The TPE procedure includes removal of antibodies, alloantibodies, immune complexes, monoclonal protein, toxins or cytokines, and involves the replenishment of a specific plasma factor. The aim of the study was to describe the clinical response to TPE in various neurological patients, and to assess the clinical response to this therapy...
2017: F1000Research
https://www.readbyqxmd.com/read/28928907/adipose-derived-stromal-cell-in-regenerative-medicine-a-review
#9
REVIEW
Reza Tabatabaei Qomi, Mohsen Sheykhhasan
The application of appropriate cell origin for utilizing in regenerative medicine is the major issue. Various kinds of stem cells have been used for the tissue engineering and regenerative medicine. Such as, several stromal cells have been employed as treat option for regenerative medicine. For example, human bone marrow-derived stromal cells and adipose-derived stromal cells (ADSCs) are used in cell-based therapy. Data relating to the stem cell therapy and processes associated with ADSC has developed remarkably in the past 10 years...
August 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28928747/modulation-of-multiple-sclerosis-and-its-animal-model-experimental-autoimmune-encephalomyelitis-by-food-and-gut-microbiota
#10
REVIEW
Ward J van den Hoogen, Jon D Laman, Bert A 't Hart
Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928746/ccl5-glutamate-cross-talk-in-astrocyte-neuron-communication-in-multiple-sclerosis
#11
REVIEW
Anna Pittaluga
The immune system (IS) and the central nervous system (CNS) are functionally coupled, and a large number of endogenous molecules (i.e., the chemokines for the IS and the classic neurotransmitters for the CNS) are shared in common between the two systems. These interactions are key elements for the elucidation of the pathogenesis of central inflammatory diseases. In recent years, evidence has been provided supporting the role of chemokines as modulators of central neurotransmission. It is the case of the chemokines CCL2 and CXCL12 that control pre- and/or post-synaptically the chemical transmission...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928713/pain-in-people-with-multiple-sclerosis-associations-with-modifiable-lifestyle-factors-fatigue-depression-anxiety-and-mental-health-quality-of-life
#12
Claudia H Marck, Alysha M De Livera, Tracey J Weiland, Pia L Jelinek, Sandra L Neate, Chelsea R Brown, Keryn L Taylor, Fary Khan, George A Jelinek
BACKGROUND: People with multiple sclerosis (MS) often experience pain, which can interfere with mobility, employment, and quality of life (QOL). METHODS: This cross-sectional study explored associations between pain, demographic, disease, and modifiable lifestyle factors in an international sample of people with MS recruited online. RESULTS: Substantial pain, of moderate/severe intensity and interfering at least moderately with work/household or enjoyment of life in the past 4 weeks, was reported by 682/2,362 (28...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28928709/insight-into-metabolic-1-h-mrs-changes-in-natalizumab-induced-progressive-multifocal-leukoencephalopathy-brain-lesions
#13
Ruth Schneider, Barbara Bellenberg, Robert Hoepner, Gisa Ellrichmann, Ralf Gold, Carsten Lukas
BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a severe complication of immunosuppressive therapies, especially of natalizumab in relapsing-remitting multiple sclerosis (MS). Metabolic changes within PML lesions have not yet been described in natalizumab-associated PML in MS patients. OBJECTIVE: To study metabolic profiles in natalizumab-associated PML lesions of MS patients by (1)H magnetic resonance spectroscopy ((1)H-MRS) at different stages during the PML course...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28928705/the-role-of-t1-weighted-derived-measures-of-neurodegeneration-for-assessing-disability-progression-in-multiple-sclerosis
#14
REVIEW
Maria A Rocca, Giancarlo Comi, Massimo Filippi
INTRODUCTION: Multiple sclerosis (MS) is characterised by the accumulation of permanent neurological disability secondary to irreversible tissue loss (neurodegeneration) in the brain and spinal cord. MRI measures derived from T1-weighted image analysis (i.e., black holes and atrophy) are correlated with pathological measures of irreversible tissue loss. Quantifying the degree of neurodegeneration in vivo using MRI may offer a surrogate marker with which to predict disability progression and the effect of treatment...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28928026/an-online-resource-to-promote-vocational-interests-among-job-seekers-with-multiple-sclerosis-a-randomized-controlled-trial-in-australia
#15
Diana Dorstyn, Rachel Roberts, Gregory Murphy, Ian Kneebone, Ashley Craig, Christine Migliorini
OBJECTIVE: To provide a preliminary evaluation of the effectiveness of an on-line resource for job-seekers with multiple sclerosis. DESIGN: Randomized controlled design. SETTING: Community-dwelling cohort in Australia. PARTICIPANTS: Forty-seven adults with relapsing-remitting or progressive MS accessed an email-delivered, 7-module resource - 'Work and MS' - over a 4-week period. Fifty wait-list control participants were offered the opportunity to access 'Work and MS' 4 weeks post-enrolment...
September 16, 2017: Archives of Physical Medicine and Rehabilitation
https://www.readbyqxmd.com/read/28927886/tnfrsf1a-and-mefv-mutations-in-childhood-onset-multiple-sclerosis
#16
Astrid Blaschek, Rüdiger V Kries, Peter Lohse, Kristina Huss, Katharina Vill, Bernd H Belohradsky, Florian Heinen, Wolfgang Müller-Felber, Tania Kümpfel
To investigate frequency and phenotype of TNFRSF1A and MEFV mutations in childhood-onset multiple sclerosis (MS). Twenty-nine clinically well characterized patients were investigated for mutations in exons 2, 3, 4, and 6 of the TNFRSF1A gene and in exons 2, 3, 9, 10 of the MEFV gene. Standardized morbidity ratio (SMR) was used to assess whether the number of observed mutations was higher than expected. Eleven out of 29 patients tested positive for mutations. Heterozygosity for the TNFRSF1A R92Q (rs4149584) variant was found in 6/11 mutation-positive patients...
September 1, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/28926943/monoclonal-antibodies-in-preclinical-eae-models-of-multiple-sclerosis-a-systematic-review
#17
REVIEW
Katja Schmitz, Gerd Geisslinger, Irmgard Tegeder
Monoclonal antibodies (mAb) are promising therapeutics in multiple sclerosis and multiple new candidates have been developed, hence increasing the need for some agreement for preclinical mAb studies. We systematically analyzed publications of experimental autoimmune encephalomyelitis (EAE) studies showing effects of monoclonal antibodies. A PubMed search retrieved 570 records, out of which 122 studies with 253 experiments were eligible based on experimental design, number of animals and presentation of time courses of EAE scores...
September 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28926869/purification-and-characterization-of-the-soluble-form-of-the-receptor-for-advanced-glycation-end-products-srage-a-novel-fast-economical-and-convenient-method
#18
Varun Kumar, Alba Sulaj, Thomas Fleming, Peter P Nawroth
The receptor for advanced glycation end-products (RAGE) is a multi-ligand receptor which belongs to the pattern recognition receptor family and can bind to various ligands such as advanced glycation end-products (AGEs), members of the S100 protein family, glycosaminoglycans, amyloid β peptides, high-mobility group box-1 (HMGB1) and nucleic acids through its extracellular domain. The RAGE-ligand interaction leads to the activation of MAP kinase and NF-kB signaling pathways. Further ligand-induced up-regulation of RAGE is involved in various patho-physiological situations including late diabetic complications, Alzheimer disease and several other neurodegenerative diseases...
September 19, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28926740/immunomodulation-in-multiple-sclerosis-promises-and-pitfalls
#19
REVIEW
Calliope A Dendrou, Lars Fugger
Multiple sclerosis (MS) afflicts about 2.5 million people globally and poses a major personal and socioeconomic burden. The recognition of MS as an inflammatory disease, characterized by infiltration of immune cells into the central nervous system, has spurred research into the autoimmune etiology of the condition and has provided the rationale for its treatment through immunomodulation. Experience with immunotherapies in MS to date has suggested a disparity between the observed immune cell infiltration and the progressive loss of neurons...
September 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28926646/vascular-hypoperfusion-in-acute-optic-neuritis-is-a-potentially-new-neurovascular-model-for-demyelinating-diseases
#20
Ta-Ching Chen, Chao-Yuan Yeh, Chao-Wen Lin, Chung-May Yang, Chang-Hao Yang, I-Hung Lin, Pao-Yang Chen, Jung-Yu Cheng, Fung-Rong Hu
PURPOSE: Optic neuritis is highly correlated with multiple sclerosis and is a major cause of acute visual loss and long-term neuronal degeneration. Primary cerebral hypoperfusion has been reported in brain demyelinating diseases. This study investigated whether peripapillary perfusion is changed in patients with acute optic neuritis (AON). METHODS: This three-year cohort study was conducted from September 1 2012, to August 31, 2015. Two hundred and forty-one patients with non-glaucomatous acute optic neuropathy were screened, and 42 non-highly myopic patients who had suffered their first episode of unilaterally idiopathic AON were studied...
2017: PloS One
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