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https://www.readbyqxmd.com/read/29185135/disease-modifying-treatments-modulate-myeloid-cells-in-multiple-sclerosis-patients
#1
Gloria Dalla Costa, Annamaria Finardi, Livia Garzetti, Tiziana Carandini, Giancarlo Comi, Vittorio Martinelli, Roberto Furlan
The role of myeloid cells in the pathogenesis of MS is determined by the polarization they acquire after activation, and mediated by release of extracellular vesicles (MVs). We assessed the effects of treatments for MS on activation and polarization of myeloid cells. MVs levels and markers of polarization of myeloid cells have been assessed at baseline and up to 6 months after the start of a MS treatment. Patients had higher levels of MVs than controls, and these increased significantly over 6 months under natalizumab...
November 28, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/29180839/triggering-receptor-expressed-on-myeloid-cells-2-overexpression-inhibits-proinflammatory-cytokines-in-lipopolysaccharide-stimulated-microglia
#2
Xiaobao Zhang, Fang Yan, Jizheng Cui, Yong Wu, Hengfei Luan, Miaomiao Yin, Zhibin Zhao, Jiying Feng, Jinwei Zhang
Microglia play an important role in mediating inflammatory processes in the central nervous system (CNS). Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglia-specific receptor and could decrease neuropathology in Alzheimer's disease (AD). However, the detailed mechanism remains unclear. This study was designed to elucidate the effect of TREM2 on microglia. We showed that lipopolysaccharide (LPS) stimulation significantly increases proinflammatory cytokines and suppressed TREM2 in microglia...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29177109/exome-sequencing-of-extended-families-with-alzheimer-s-disease-identifies-novel-genes-implicated-in-cell-immunity-and-neuronal-function
#3
H N Cukier, B K Kunkle, K L Hamilton, S Rolati, M A Kohli, P L Whitehead, J Jaworski, J M Vance, M L Cuccaro, R M Carney, J R Gilbert, L A Farrer, E R Martin, G W Beecham, J L Haines, M A Pericak-Vance
Objective: Alzheimer's disease (AD) is a neurodegenerative disorder for which more than 20 genetic loci have been implicated to date. However, studies demonstrate not all genetic factors have been identified. Therefore, in this study we seek to identify additional rare variants and novel genes potentially contributing to AD. Methods: Whole exome sequencing was performed on 23 multi-generational families with an average of eight affected subjects. Exome sequencing was filtered for rare, nonsynonymous and loss-of-function variants...
August 2017: Journal of Alzheimer's Disease and Parkinsonism
https://www.readbyqxmd.com/read/29169609/microglia-mediated-neuroprotection-trem2-and-alzheimer-s-disease-evidence-from-optical%C3%A2-imaging
#4
REVIEW
Carlo Condello, Peng Yuan, Jaime Grutzendler
Recent genetic studies have provided overwhelming evidence of the involvement of microglia-related molecular networks in the pathophysiology of Alzheimer's disease (AD). However, the precise mechanisms by which microglia alter the course of AD neuropathology remain poorly understood. Here we discuss current evidence of the neuroprotective functions of microglia with a focus on optical imaging studies that have revealed a role of these cells in the encapsulation of amyloid deposits ("microglia barrier"). This barrier modulates the degree of plaque compaction, amyloid fibril surface area, and insulation from adjacent axons thereby reducing neurotoxicity...
October 14, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29142083/evidence-of-cns-%C3%AE-amyloid-deposition-in-nasu-hakola-disease-due-to-the-trem2-q33x-mutation
#5
Laura Ghezzi, Tiziana Carandini, Andrea Arighi, Chiara Fenoglio, Marina Arcaro, Milena De Riz, Anna M Pietroboni, Giorgio G Fumagalli, Paola Basilico, Alberto Calvi, Marta Scarioni, Annalisa Colombi, Maria Serpente, Giorgio Marotta, Riccardo Benti, Elio Scarpini, Daniela Galimberti
No abstract text is available yet for this article.
November 15, 2017: Neurology
https://www.readbyqxmd.com/read/29104108/high-trem2-expression-correlates-with-poor-prognosis-in-gastric-cancer
#6
Xiaojing Zhang, Wei Wang, Peng Li, Xudong Wang, Kan Ni
Triggering receptor expressed on myeloid cells 2 (TREM2) is a member of the immunoglobulin superfamily and associates with TYRO protein tyrosine kinase-binding protein at the cell membrane to form a receptor signaling complex. Gastric cancer (GC) is one of the most common human cancer in the word, we found that TREM2 expression in gastric cancer and adjacent tissues were significantly different. The goal of this study was to measure TREM2 protein and mRNA expression levels in GC tissues and evaluate their value as potential prognostic markers...
November 2, 2017: Human Pathology
https://www.readbyqxmd.com/read/29073081/trem2-deficiency-attenuates-neuroinflammation-and-protects-against-neurodegeneration-in-a-mouse-model-of-tauopathy
#7
Cheryl E G Leyns, Jason D Ulrich, Mary B Finn, Floy R Stewart, Lauren J Koscal, Javier Remolina Serrano, Grace O Robinson, Elise Anderson, Marco Colonna, David M Holtzman
Variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) were recently found to increase the risk for developing Alzheimer's disease (AD). In the brain, TREM2 is predominately expressed on microglia, and its association with AD adds to increasing evidence implicating a role for the innate immune system in AD initiation and progression. Thus far, studies have found TREM2 is protective in the response to amyloid pathology while variants leading to a loss of TREM2 function impair microglial signaling and are deleterious...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29059709/microglial-dysfunction-as-a-key-pathological-change-in-adrenomyeloneuropathy
#8
Yi Gong, Nikhil Sasidharan, Fiza Laheji, Matthew Frosch, Patricia Musolino, Rudy Tanzi, Doo Yeon Kim, Alessandra Biffi, Joseph El Khoury, Florian Eichler
OBJECTIVE: Mutations in ABCD1 cause the neurodegenerative disease, adrenoleukodystrophy, which manifests as the spinal cord axonopathy adrenomyeloneuropathy (AMN) in nearly all males surviving into adulthood. Microglial dysfunction has long been implicated in pathogenesis of brain disease, but its role in the spinal cord is unclear. METHODS: We assessed spinal cord microglia in humans and mice with AMN and investigated the role of ABCD1 in microglial activity toward neuronal phagocytosis in cell culture...
November 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29051843/alterations-in-micro-rna-messenger-rna-mirna-mrna-coupled-signaling-networks-in-sporadic-alzheimer-s-disease-ad-hippocampal-ca1
#9
V Jaber, Y Zhao, W J Lukiw
RNA sequencing, DNA microfluidic array, LED-Northern, Western immunoassay and bioinformatics analysis have uncovered a small family of up-regulated human brain enriched microRNAs (miRNAs) and down-regulated messenger RNAs (mRNAs) in short post-mortem interval (PMI) sporadic Alzheimer's disease (AD) brain. At the mRNA level, a large majority of the expression of human brain genes found to be down-regulated in sporadic AD appears to be a consequence of an up-regulation of a specific group of NF-kB-inducible microRNAs (miRNAs)...
April 2017: Journal of Alzheimer's Disease and Parkinsonism
https://www.readbyqxmd.com/read/29051087/triggering-receptor-expressed-on-myeloid-cells-2-trem2-dependent-microglial-activation-promotes-cisplatin-induced-peripheral-neuropathy-in-mice
#10
Lang-Yue Hu, Yang Zhou, Wen-Qiang Cui, Xue-Ming Hu, Li-Xia Du, Wen-Li Mi, Yu-Xia Chu, Gen-Cheng Wu, Yan-Qing Wang, Qi-Liang Mao-Ying
Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse side effect of many antineoplastic agents. Patients treated with chemotherapy often report pain and paresthesias in a "glove-and-stocking" distribution. Diverse mechanisms contribute to the development and maintenance of CIPN. However, the role of spinal microglia in CIPN is not completely understood. In this study, cisplatin-treated mice displayed persistent mechanical allodynia, sensory deficits and decreased density of intraepidermal nerve fibers (IENFs)...
October 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29040522/behavioral-and-transcriptomic-analysis-of-trem2-null-mice-not-all-knockout-mice-are-created-equal
#11
Silvia S Kang, Aishe Kurti, Kelsey E Baker, Chia-Chen Liu, Marco Colonna, Jason D Ulrich, David M Holtzman, Guojun Bu, John D Fryer
It is clear that innate immune system status is altered in numerous neurodegenerative diseases. Human genetic studies have demonstrated that Triggering Receptor Expressed in Myeloid cells 2 (TREM2) coding variants have a strong association with Alzheimer's disease (AD) and other neurodegenerative diseases. To more thoroughly understand the impact of TREM2 in vivo, we studied the behavioral and cognitive functions of wild-type (WT) and Trem2-/- (KO) mice during basal conditions and brain function in the context of innate immune stimulation with peripherally administered lipopolysaccharide (LPS)...
October 11, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29037207/trem2-deficiency-exacerbates-tau-pathology-through-dysregulated-kinase-signaling-in-a-mouse-model-of-tauopathy
#12
Shane M Bemiller, Tyler J McCray, Kevin Allan, Shane V Formica, Guixiang Xu, Gina Wilson, Olga N Kokiko-Cochran, Samuel D Crish, Cristian A Lasagna-Reeves, Richard M Ransohoff, Gary E Landreth, Bruce T Lamb
BACKGROUND: Genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) confer increased risk of developing late-onset Alzheimer's Disease (LOAD) and other neurodegenerative disorders. Recent studies provided insight into the multifaceted roles of TREM2 in regulating extracellular β-amyloid (Aβ) pathology, myeloid cell accumulation, and inflammation observed in AD, yet little is known regarding the role of TREM2 in regulating intracellular microtubule associated protein tau (MAPT; tau) pathology in neurodegenerative diseases and in AD, in particular...
October 16, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29036448/il6-secretion-from-alternatively-activated-macrophages-promotes-the-migration-of-endometriotic-epithelial-cells
#13
Jeong-Hwa Woo, Yeong-In Yang, Ji-Hye Ahn, Youn Seok Choi, Jung-Hye Choi
Accumulating evidence has suggested an interaction between endometriotic cells and macrophages in the endometriotic microenvironment and the potential role of this interaction in the pathogenesis of endometriosis. However, how endometriotic cells communicate with macrophages to influence their function is poorly understood. In the present study, we found that the mRNA expression and production of CC chemokine ligand 2 (CCL2) were much higher in human endometriotic epithelial cells (11Z and 12Z) than those in human endometrial epithelial cells (HES)...
October 4, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29017955/triggering-receptor-expressed-on-myeloid-cells-2-expression-tracks-with-m2-like-macrophage-activity-and-disease-severity-in%C3%A2-copd
#14
Derek E Byers, Kangyun Wu, Geoffrey Dang-Vu, Xiaohua Jin, Eugene Agapov, Xiaofeng Zhang, John T Battaile, Kenneth Schechtman, Roger Yusen, Richard A Pierce, Michael J Holtzman
BACKGROUND: Cell and animal models show a key role for Triggering Receptor Expressed on Myeloid Cells (TREM)-2 in chronic airway disease after viral infection, but comparable evidence in humans still needs to be established. METHODS: Lung tissue samples were obtained from lung transplant recipients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD (n = 16), nontransplantable donor lung tissues (n = 10), and resected lung tissues from patients at risk or with GOLD stage I through IV (n = 72) and were assessed for TREM-2 and TREM-1 messenger RNA (mRNA), protein expression, and other markers of a type 2 immune response...
October 7, 2017: Chest
https://www.readbyqxmd.com/read/28987033/trem2-expression-in-the-human-brain-a-marker-of-monocyte-recruitment
#15
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/28978423/trem2-keeping-microglia-fit-during-good-times-and-bad
#16
Soyon Hong, Beth Stevens
Microglia are the macrophages of the brain and play an important role in Alzheimer's disease (AD). In Cell, Ulland et al. (2017) recently reported that mutations in TREM2, a protein implicated in AD, disrupt microglial energy state and function, thus sabotaging the microglia's ability to defend the brain against amyloid plaques.
October 3, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28930663/the-trem2-apoe-pathway-drives-the-transcriptional-phenotype-of-dysfunctional-microglia-in-neurodegenerative-diseases
#17
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/28930654/a-tale-of-two-genes-microglial-apoe-and-trem2
#18
Anna A Pimenova, Edoardo Marcora, Alison M Goate
Microglial cell function is implicated in the etiology of Alzheimer's disease by human genetics. In this issue of Immunity, Krasemann et al. (2017) describe a gene expression signature associated with an APOE- and TREM2-dependent response of microglia to brain tissue damage that accumulates in aging and disease, defining an axis that might be amenable to therapeutic targeting.
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28923481/adam17-is-the-main-sheddase-for-the-generation-of-human-triggering-receptor-expressed-in-myeloid-cells-htrem2-ectodomain-and-cleaves-trem2-after-histidine-157
#19
Dominik Feuerbach, Patrick Schindler, Carmen Barske, Stefanie Joller, Edwige Beng-Louka, Katie A Worringer, Sravya Kommineni, Ajamete Kaykas, Daniel J Ho, Chaoyang Ye, Karl Welzenbach, Gaelle Elain, Laurent Klein, Irena Brzak, Anis K Mir, Christopher J Farady, Reiner Aichholz, Simone Popp, Nathalie George, Ulf Neumann
Triggering receptor expressed in myeloid cells (TREM2) is a member of the immunoglobulin superfamily and is expressed in macrophages, dendritic cells, microglia, and osteoclasts. TREM2 plays a role in phagocytosis, regulates release of cytokine, contributes to microglia maintenance, and its ectodomain is shed from the cell surface. Here, the question was addressed at which position sheddases cleave TREM2 and what are the proteases involved in this process. Using both pharmacological and genetic approaches we report that the main protease contributing to the release of TREM2 ectodomain is ADAM17, (a disintegrin and metalloproteinase domain containing protein, also called TACE, TNFα converting enzyme) while ADAM10 plays a minor role...
November 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28912710/key-aging-associated-alterations-in-primary-microglia-response-to-beta-amyloid-stimulation
#20
Cláudia Caldeira, Carolina Cunha, Ana R Vaz, Ana S Falcão, Andreia Barateiro, Elsa Seixas, Adelaide Fernandes, Dora Brites
Alzheimer's disease (AD) is characterized by a progressive cognitive decline and believed to be driven by the self-aggregation of amyloid-β (Aβ) peptide into oligomers and fibrils that accumulate as senile plaques. It is widely accepted that microglia-mediated inflammation is a significant contributor to disease pathogenesis; however, different microglia phenotypes were identified along AD progression and excessive Aβ production was shown to dysregulate cell function. As so, the contribution of microglia to AD pathogenesis remains to be elucidated...
2017: Frontiers in Aging Neuroscience
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