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https://www.readbyqxmd.com/read/28726484/annals-express-experience-with-newer-central-nervous-system-autoantibodies
#1
Abid Karim, Saiju Jacob
In the last decade, a large number of neuronal cell-surface antibodies have been described which are responsible for a range of neuroimmunological central nervous system disorders. Unlike the paraneoplastic antibodies which target intracellular antigens, these antibodies appear to be pathogenic and hence identification and prompt treatment can make a substantial impact on clinical outcomes of these patients. We review the common antibodies against the ionotropic Glutamate receptors (NMDAR, AMPAR), metabotropic Glutamate receptors (mGluR1 and mGluR5), voltage gated potassium channel-complex proteins (LGI1, CASPR2), and other antibodies targeted against Glycine receptor, Glutamic acid decarboxylase (GAD), Gamma Amino Butyric Acid B (GABAB), Dopamine-2-receptor (D2R) and Dipeptidyl-peptidase-like protein 6 (DPPX)...
January 1, 2017: Annals of Clinical Biochemistry
https://www.readbyqxmd.com/read/28724750/disruption-of-a-structurally-important-extracellular-element-in-the-glycine-receptor-leads-to-decreased-synaptic-integration-and-signaling-resulting-in-severe-startle-disease
#2
Natascha Schaefer, Alexandra Berger, Johannes van Brederode, Fang Zheng, Yan Zhang, Sophie Leacock, Laura Littau, Sibylle Jablonka, Sony Malhotra, Maya Topf, Friederike Winter, Daria Davydova, Joseph W Lynch, Christopher J Paige, Christian Alzheimer, Robert J Harvey, Carmen Villmann
Functional impairments or trafficking defects of inhibitory glycine receptors (GlyRs) have been linked to human hyperekplexia/startle disease and autism spectrum disorder. We found that lack of synaptic integration of GlyRs, together with disrupted receptor function is responsible for a lethal startle phenotype in a novel spontaneous mouse mutant shaky, caused by a missense mutation Q177K located in the extracellular β8-β9 loop of the GlyR α1 subunit. Recently, structural data provided evidence that the flexibility of the β8-β9 loop is crucial for conformational transitions during opening and closing of the ion channel and represents a novel allosteric binding site in cys-loop receptors...
July 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28723958/can-single-molecule-localization-microscopy-be-used-to-map-closely-spaced-rgd-nanodomains
#3
Mahdie Mollazade, Thibault Tabarin, Philip R Nicovich, Alexander Soeriyadi, Daniel J Nieves, J Justin Gooding, Katharina Gaus
Cells sense and respond to nanoscale variations in the distribution of ligands to adhesion receptors. This makes single molecule localization microscopy (SMLM) an attractive tool to map the distribution of ligands on nanopatterned surfaces. We explore the use of SMLM spatial cluster analysis to detect nanodomains of the cell adhesion-stimulating tripeptide arginine-glycine-aspartic acid (RGD). These domains were formed by the phase separation of block copolymers with controllable spacing on the scale of tens of nanometers...
2017: PloS One
https://www.readbyqxmd.com/read/28716844/microglia-control-the-glycinergic-but-not-the-gabaergic-synapses-via-prostaglandin-e2-in-the-spinal-cord
#4
Yasmine Cantaut-Belarif, Myriam Antri, Rocco Pizzarelli, Sabrina Colasse, Ilaria Vaccari, Sylvia Soares, Marianne Renner, Radhouane Dallel, Antoine Triller, Alain Bessis
Microglia control excitatory synapses, but their role in inhibitory neurotransmission has been less well characterized. Herein, we show that microglia control the strength of glycinergic but not GABAergic synapses via modulation of the diffusion dynamics and synaptic trapping of glycine (GlyR) but not GABAA receptors. We further demonstrate that microglia regulate the activity-dependent plasticity of glycinergic synapses by tuning the GlyR diffusion trap. This microglia-synapse cross talk requires production of prostaglandin E2 by microglia, leading to the activation of neuronal EP2 receptors and cyclic adenosine monophosphate-dependent protein kinase...
July 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28712640/resident-calmodulin-primes-nmda-receptors-for-ca-2-dependent-inactivation
#5
Gary J Iacobucci, Gabriela K Popescu
N-methyl-d-aspartate (NMDA) receptors are glutamate- and glycine-gated channels that flux Na(+) and Ca(2+) into postsynaptic neurons during synaptic transmission. The resulting intracellular Ca(2+) transient is essential to physiological and pathological processes related to synaptic development, plasticity, and apoptosis. It also engages calmodulin (CaM) to reduce subsequent NMDA receptor activity in a process known as Ca(2+)-dependent inactivation (CDI). Here, we used whole-cell electrophysiology to measure CDI and computational modeling to dissect the sequence of events that underlies it...
July 14, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28711937/magnetic-resonance-metabolic-profiling-of-estrogen-receptor-positive-breast-cancer-correlation-with-currently-used-molecular-markers
#6
Ji Soo Choi, Dahye Yoon, Ja Seung Koo, Siwon Kim, Vivian Youngjean Park, Eun-Kyung Kim, Suhkmann Kim, Min Jung Kim
Estrogen receptor (ER)-positive breast cancers overall have a good prognosis, however, some patients suffer relapses and do not respond to endocrine therapy. The purpose of this study was to determine whether there are any correlations between high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) metabolic profiles of core needle biopsy (CNB) specimens and the molecular markers currently used in patients with ER-positive breast cancers. The metabolic profiling of CNB samples from 62 ER-positive cancers was performed by HR-MAS MRS...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28709671/mechanism-and-properties-of-positive-allosteric-modulation-of-n-methyl-d-aspartate-receptors-by-6-alkyl-2-naphthoic-acid-derivatives
#7
Kiran Sapkota, Mark W Irvine, Guangyu Fang, Erica S Burnell, Neil Bannister, Arturas Volianskis, Georgia R Culley, Shashank M Dravid, Graham L Collingridge, David E Jane, Daniel T Monaghan
The theory that N-methyl-d-aspartate receptor (NMDAR) hypofunction is responsible for the symptoms of schizophrenia is well supported by many pharmacological and genetic studies. Accordingly, positive allosteric modulators (PAMs) that augment NMDAR signaling may be useful for treating schizophrenia. Previously we have identified several NMDAR PAMs containing a carboxylic acid attached to naphthalene, phenanthrene, or coumarin ring systems. In this study, we describe several functional and mechanistic properties of UBP684, a 2-naphthoic acid derivative, which robustly potentiates agonist responses at each of the four GluN1a/GluN2 receptors and at neuronal NMDARs...
July 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28704758/deconstruction-reconstruction-approach-to-analyze-the-essential-structural-elements-of-tetrahydro-3-benzazepine-based-antagonists-of-glun2b-subunit-containing-nmda-receptors
#8
Sougata Dey, Louisa Temme, Julian A Schreiber, Dirk Schepmann, Bastian Frehland, Kirstin Lehmkuhl, Nathalie Strutz-Seebohm, Guiscard Seebohm, Bernhard Wünsch
The role of the phenolic and benzylic OH moieties for the interaction of tetrahydro-3-benzazepine-1,7-diol 3d with GluN2B subunit containing NMDA receptors was analyzed by their stepwise removal. Elimination of trifluormethanesulfinate from 10 and 13 represent the key steps in the synthesis. Removal of phenolic OH moiety led to 5-fold reduced GluN2B affinity of 4d compared with 3d. Additional removal of the benzylic OH moiety (5d) resulted in further reduced GluN2B affinity but increased σ1 and σ2 affinities...
July 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28701225/association-of-schizophrenia-onset-age-and-white-matter-integrity-with-treatment-effect-of-d-cycloserine-a-randomized-placebo-controlled-double-blind-crossover-study
#9
Kazuo Takiguchi, Akihito Uezato, Michio Itasaka, Hidenori Atsuta, Kenji Narushima, Naoki Yamamoto, Akeo Kurumaji, Makoto Tomita, Kazunari Oshima, Kosaku Shoda, Mai Tamaru, Masahito Nakataki, Mitsutoshi Okazaki, Sayuri Ishiwata, Yasuyoshi Ishiwata, Masato Yasuhara, Kunimasa Arima, Tetsuro Ohmori, Toru Nishikawa
BACKGROUND: It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. METHODS: We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time...
July 12, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28698140/n-arachidonoyl-glycine-another-endogenous-agonist-of-gpr55
#10
Linda Console-Bram, Sandra M Ciuciu, Pingwei Zhao, Robert E Zipkin, Eugen Brailoiu, Mary E Abood
Interest in lipoamino acids as endogenous modulators of G-protein coupled receptors has escalated due to their involvement in a variety of physiologic processes. In particular, a role for these amino acid conjugates has emerged in the endocannabinoid system. The study presented herein investigated the effects of N-arachidonoyl glycine (NAGly) on a candidate endocannabinoid receptor, GPR55. Our novel findings reveal that NAGly induces concentration dependent increases in calcium mobilization and mitogen-activated protein kinase activities in HAGPR55/CHO cells...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28676256/neurotoxicity-of-propofol-on-rat-hypoglossal-motoneurons-in-vitro
#11
Laura Monni, Filippo Ghezzi, Silvia Corsini, Andrea Nistri
Although propofol is a widely used intravenous general anaesthetic, many studies report its toxic potential, particularly on the developing central nervous system. We investigated its action on hypoglossal motoneurons (HMs) that control two critical functions in neonates, namely tongue muscle activity and airway patency. Thus, clinically relevant concentrations of propofol (1 and 5μM) were applied (4h) to neonatal rat brainstem slices to evaluate the expression of apoptosis-inducing factor (AIF) as biomarker of toxicity...
July 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28674368/thymoma-associated-progressive-encephalomyelitis-with-rigidity-and-myoclonus-perm-with-myasthenia-gravis
#12
Satoshi Morise, Masataka Nakamura, Jun-Ichi Morita, Kousuke Miyake, Takenobu Kunieda, Satoshi Kaneko, Hirofumi Kusaka
We report a case of a 72-year-old woman who initially presented with symptoms of bulbar myasthenia and was positive for anti-acetylcholine receptor antibodies. She subsequently developed painful muscle spasms, myoclonus, and stiffness. Thymoma was detected, and both anti-glycine receptor and anti-glutamic acid decarboxylase antibodies were found. She was diagnosed with thymoma-associated progressive encephalomyelitis with rigidity and myoclonus (PERM). She experienced marked improvement after thymectomy followed by plasma exchange and intravenous immunoglobulin and prednisolone...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28671605/glycine-binding-site-stimulants-of-nmda-receptors-alleviate-extrapyramidal-motor-disorders-by-activating-the-nigrostriatal-dopaminergic-pathway
#13
Saki Shimizu, Shunsaku Sogabe, Ryoto Yanagisako, Akiyoshi Inada, Megumi Yamanaka, Higor A Iha, Yukihiro Ohno
Dysfunction of the N-methyl-d-aspartate (NMDA) receptor has been implicated in the pathogenesis of schizophrenia. Although agonists for the glycine-binding sites of NMDA receptors have potential as new medication for schizophrenia, their modulation of antipsychotic-induced extrapyramidal side effects (EPS) has not yet been clarified. We herein evaluated the effects of glycine-binding site stimulants of NMDA receptors on antipsychotic-induced EPS in mice and rats. d-cycloserine (DCS) and d-serine significantly improved haloperidol (HAL)-induced bradykinesia in mice, whereas glycine showed no effects...
July 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28669824/floppy-but-not-sloppy-interaction-mechanism-of-fg-nucleoporins-and-nuclear-transport-receptors
#14
REVIEW
Iker Valle Aramburu, Edward A Lemke
The nuclear pore complex (NPC) forms a permeability barrier between the nucleus and the cytoplasm. Molecules that are able to cross this permeability barrier encounter different disordered phenylalanine glycine rich nucleoporins (FG-Nups) that act as a molecular filter and regulate the selective NPC crossing of biomolecules. In this review, we provide a current overview regarding the interaction mechanism between FG-Nups and the carrier molecules that recognize and enable the transport of cargoes through the NPC aiming to understand the general molecular mechanisms that facilitate the nucleocytoplasmic transport...
June 29, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28669667/transhepatic-bile-acid-kinetics-in-pigs-and-humans
#15
Hannah M Eggink, F Samuel van Nierop, Marieke G Schooneman, Anita Boelen, Andries Kalsbeek, Martijn Koehorst, Gabriella A M Ten Have, L Maurits de Brauw, Albert K Groen, Johannes A Romijn, Nicolaas E P Deutz, Maarten R Soeters
BACKGROUND & AIMS: Bile acids (BAs) play a key role in lipid uptake and metabolic signalling in different organs including gut, liver, muscle and brown adipose tissue. Portal and peripheral plasma BA concentrations increase after a meal. However, the exact kinetics of postprandial BA metabolism have never been described in great detail. We used a conscious porcine model to investigate postprandial plasma concentrations and transorgan fluxes of BAs, glucose and insulin using the para-aminohippuric acid dilution method...
June 19, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28664727/mutational-replacements-at-the-glycine-hinge-of-the-escherichia-coli-chemoreceptor-tsr-support-a-signaling-role-for-the-c-helix-residue
#16
Andrea Pedetta, Diego Ariel Massazza, María Karina Herrera Seitz, Claudia Alicia Studdert
Bacterial chemoreceptors are dimeric membrane proteins that transmit signals from a periplasmic ligand-binding domain to the interior of the cells. The highly conserved cytoplasmic domain consists of a long hairpin that in the dimer forms a four-helix coiled-coil bundle. The central region of the bundle couples changes in helix packing that occur in the membrane proximal region to the signaling tip, controlling the activity of an associated histidine kinase. This subdomain contains certain glycine residues that are postulated to form a hinge in chemoreceptors from enteric bacteria and have been largely postulated to play a role in the coupling mechanism, and/or in the formation of higher-order chemoreceptor assemblies...
July 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28659933/genome-wide-identification-and-expression-profiling-of-ethylene-receptor-genes-during-soybean-nodulation
#17
Youning Wang, Jinhong Yuan, Wei Yang, Lin Zhu, Chao Su, Xiaodi Wang, Haiyan Wu, Zhengxi Sun, Xia Li
It has long been known that the gaseous plant hormone ethylene plays a key role in nodulation in legumes. The perception of ethylene by a family of five membrane-localized receptors is necessary to trigger the ethylene signaling pathway, which regulates various biological responses in Arabidopsis. However, a systematic analysis of the ethylene receptors in leguminous plants and their roles in nodule development is lacking. In this study, we performed a characterization of ethylene receptor genes based on the latest Glycine max genome sequence and a public microarray database...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28658579/connecting-protein-conformation-and-dynamics-with-ligand-receptor-binding-using-three-color-f%C3%A3-rster-resonance-energy-transfer-tracking
#18
Mark Kastantin, David Faulón Marruecos, Navdeep Grover, Sean Yu McLoughlin, Daniel K Schwartz, Joel L Kaar
Specific binding between biomolecules, i.e., molecular recognition, controls virtually all biological processes including the interactions between cells and biointerfaces, both natural and synthetic. Such binding often relies on the conformation of biomacromolecules, which can be highly heterogeneous and sensitive to environmental perturbations, and therefore difficult to characterize and control. An approach is demonstrated here that directly connects the binding kinetics and stability of the protein receptor integrin αvβ3 to the conformation of the ligand fibronectin (FN), which are believed to control cellular mechanosensing...
July 12, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28649199/glyx-13-a-nmda-receptor-glycine-site-functional-partial-agonist-attenuates-cerebral-ischemia-injury-in-vivo-and-vitro-by-differential-modulations-of-nmda-receptors-subunit-components-at-different-post-ischemia-stage-in-mice
#19
Chen Zheng, Zhi H Qiao, Meng Z Hou, Nan N Liu, Bin Fu, Ran Ding, Yuan Y Li, Liang P Wei, Ai L Liu, Hui Shen
Excessive activation of NMDA receptors (NMDARs) is implicated in pathological synaptic plasticity also known as post-ischemic long-term potentiation (i-LTP) which was produced by glutamate mediated excitotoxicity after stroke. In the past decades, many NMDARs inhibitors failed in clinical investigations due to severe psychotomimetic side effects. GLYX-13 is a NMDAR modulator with glycine site partial agonist properties and has potential protective effects on ischemic neuronal death. However, the underlying molecular mechanism of GLYX-13 attenuating the ischemic neuronal damage remains elusive...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28620235/a-non-ionotropic-activity-of-nmda-receptors-contributes-to-glycine-induced-neuroprotection-in-cerebral-ischemia-reperfusion-injury
#20
Juan Chen, Rong Hu, Huabao Liao, Ya Zhang, Ruixue Lei, Zhifeng Zhang, Yang Zhuang, Yu Wan, Ping Jin, Hua Feng, Qi Wan
NMDA receptor (NMDAR) is known for its ionotropic function. But recent evidence suggests that NMDAR also has a non-ionotropic property. To determine the role of non-ionotropic activity of NMDARs in clinical relevant conditions, we tested the effect of glycine, a co-agonist of NMDARs, in rat middle cerebral artery occlusion (MCAO), an animal model of cerebral ischemia-reperfusion injury after the animals were injected with the NMDAR channel blocker MK-801 and the glycine receptor antagonist strychnine. We show that glycine reduces the infarct volume in the brain of ischemic stroke animals pre-injected with MK-801 and strychnine...
June 15, 2017: Scientific Reports
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