Search results for "glutamate receptor"
showing 10 items of 219 documents
Membrane breakdown in acute and chronic neurodegeneration: focus on choline-containing phospholipids.
2000
Breakdown of cellular membranes is a characteristic feature of neuronal degeneration in acute (stroke) and chronic (senile dementia) neurological disorders. The present review summarizes recent experimental and clinical work which concentrated on changes of choline-containing phospholipids as indicators of neuronal membrane breakdown. Experimental studies identified glutamate release, calcium influx, and activation of cellular phospholipase A2 (PLA2) as important steps initiating membrane breakdown in cultured neurons or brain slices under hypoxic or ischemic conditions. Proton NMR studies have shown an elevation of choline-containing compounds in the brain of Alzheimer patients while neuro…
l-Glutamate receptor binding in bovine retina
1982
Using a centrifugation technique saturable specific [ 3 H]glutamate binding in bovine retina could be demonstrated. Scatchard analysis revealed only one population of binding sites with a dissociation constant of about 3 μ m and a maximal number of binding sites of about 0·2 pmol/mg retinal protein. Several glutamic acid analogues inhibit specific [ 3 H]glutamate binding in bovine retina with half-maximal inhibitory concentrations similar to those reported in other areas of the CNS. Specific [ 3 H]glutamate binding and sodium dependent synaptosomal uptake of glutamate are largely concentrated in the P2 fraction of bovine retina homogenates consisting of conventionally sized synaptosomes. Th…
Pro-inflammatory T helper 17 directly harms oligodendrocytes in neuroinflammation.
2021
Significance Multiple sclerosis (MS) is a neuroinflammatory, demyelinating disease that represents one of the most frequent causes of irreversible disability in young adults. Treatment options to halt disability are limited. We discovered that T helper (Th)17 cells in contact with oligodendrocytes produce higher levels of glutamate and induce significantly greater oligodendrocyte damage than their Th2 counterpart. Blockade of CD29, which is linked to glutamate release pathways and expressed in high levels on Th17 cells, preserved human oligodendrocyte processes from Th17-mediated injury. Our data thus provide evidence for the direct and deleterious attack of Th17 cells on the myelin compart…
Neuronal expression and regulation of rat inhibitor of apoptosis protein-2 by kainic acid in the rat brain
2002
Inhibitors of apoptosis proteins (IAPs) define a protein family with the ability to counteract cell death by the inhibition of different caspases activated during apoptosis. These proteins are present in different cells, however, the function and roles of IAPs in brain tissue are not fully understood. We report here that RIAP-2, the rat homologue of human cIAP-1/HIAP-2, is expressed in different areas of rat brain as shown by in situ hybridization and immunohistochemistry. Brain regions with relatively high expression of RIAP-2 mRNA included cortex, cerebellum and different subregions of rat hippocampus. Double labelling using a specific anti-RIAP antibody and markers for neurons and glial …
Excitotoxin-induced changes in transglutaminase during differentiation of cerebellar granule cells
2002
Excitotoxicity induced by NMDA receptor stimulation is able to increase the activity of many enzymes involved in neuronal cell death. Primary cultures of rat cerebellar granule cells were used to elucidate the role of transglutaminase reaction in the excitotoxic cell response, and to evaluate the role of glutamate receptors in cell survival and degeneration. Granule neurons, maintained in vitro for two weeks, were exposed to NMDA at different stages of differentiation. Following NMDA receptor activation, increases in transglutaminase activity were observed in cell cultures. The levels of enzyme activity were higher in cells at 5 days in vitro than in those at 8-9 or 13-14 days in vitro. Mor…
Integrative proteomics: functional and molecular characterization of a particular glutamate-related neuregulin isoform.
2005
Glutamate is the major excitatory neurotransmitter in the mammalian brain and is related to memory by calcium-conducting receptors. Neuregulins have emerged as long-term modulating molecules of synaptic signaling by glutamate receptors, playing a role in some cognition/memory-related disorders and moreover being part of transient functional microdomains, called lipid rafts. Here we characterize one specific isoform of neuregulin as a central biomarker for glutamate-related signaling, integrating results from in vitro and in vivo models by a differential functional and proteomic approach.
Antagonists and agonists at the glycine site of the NMDA receptor for therapeutic interventions.
2003
For decades neuroreceptor research has focused on the development of NMDA glycine-site antagonists, after Johnson and Ascher found out in 1987 about the co-agonistic character of this achiral amino acid at the NMDA receptor. Contrary to the inhibitory glycine receptor (glycine(A)) the glycine binding site on the NMDA receptor (glycine(B)) is strychnine-insensitive. A great diversity of diseases showing a disturbed glutamate neurotransmission have been linked to the NMDA receptor. Glycine site antagonists have been investigated for acute diseases like stroke and head trauma as well as chronic ones like dementia and chronic pain.
The Proteoglycan NG2 Is Complexed with α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors by the PDZ Glutamate Receptor Interactio…
2003
The proteoglycan NG2 is expressed by immature glial cells in the developing and adult central nervous system. Using the COOH-terminal region of NG2 as bait in a yeast two-hybrid screen, we identified the glutamate receptor interaction protein GRIP1, a multi-PDZ domain protein, as an interacting partner. NG2 exhibits a PDZ binding motif at the extreme COOH terminus which binds to the seventh PDZ domain of GRIP1. In addition to the published expression in neurons, GRIP1 is expressed by immature glial cells. GRIP1 is known to bind to the GluRB subunit of the AMPA glutamate receptor expressed by subpopulations of neurons and immature glial cells. In cultures of primary oligodendrocytes, cells c…
Optimization of a LC method for the enantioseparation of a non-competitive glutamate receptor antagonist, by experimental design methodology
2006
Abstract The aim of this work was to obtain the direct optical resolution of a new glutamate receptor antagonist (( p -chloro)1-aryl-6,7,-dimethoxy-1,2,3,4-tetrahydroisoquinoline, PS3), by liquid chromatography on Chiralcel ® OD column. A response surface methodology (RSM) was employed to optimize the enantiomeric separation of the racemate with the lowest number of experiments; in particular, a face-centred design (FCD) was applied to evaluate the influence of critical parameters on the experimental response. Furthermore, in order to find the best compromise between several responses, a multicriteria decision-making approach, the Derringer's desirability function, was successful to simulta…
A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics
2011
Glutamate excitotoxicity leads to fragmented mitochondria in neurodegenerative diseases, mediated by nitric oxide and S-nitrosylation of dynamin-related protein 1, a mitochondrial outer membrane fission protein. Optic atrophy gene 1 (OPA1) is an inner membrane protein important for mitochondrial fusion. Autosomal dominant optic atrophy (ADOA), caused by mutations in OPA1, is a neurodegenerative disease affecting mainly retinal ganglion cells (RGCs). Here, we showed that OPA1 deficiency in an ADOA model influences N-methyl-D-aspartate (NMDA) receptor expression, which is involved in glutamate excitotoxicity and oxidative stress. Opa1enu/+mice show a slow progressive loss of RGCs, activation …