161 results
Search Results
2. The paper electrophoretic distribution of soluble proteins in different regions of human brain.
- Author
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ROBERTSON DM
- Subjects
- Brain, Brain Chemistry, Proteins chemistry
- Published
- 1960
- Full Text
- View/download PDF
3. Protein incorporation and axoplasmic flow in motoneuron fibres following intra-cord injection of labelled leucine.
- Author
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Ochs S, Johnson J, and Ng MH
- Subjects
- Animals, Autoradiography, Carbon Isotopes, Cats, Centrifugation, Chromatography, Paper, Injections, Neural Conduction, Phosphorus Isotopes, Trichloroacetic Acid, Tritium, Axons metabolism, Leucine metabolism, Motor Neurons metabolism, Phosphorus metabolism, Proteins metabolism, Puromycin pharmacology, Spinal Cord metabolism
- Published
- 1967
- Full Text
- View/download PDF
4. Interaction of curare and soluble brain proteins demonstrated by the technique of crossing paper electrophoresis
- Author
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Kazutami Kiyota
- Subjects
Cellular and Molecular Neuroscience ,Curare ,Chromatography ,Chemistry ,medicine ,Brain ,Proteins ,Electrophoresis, Paper ,Paper electrophoresis ,Biochemistry ,medicine.drug - Published
- 1962
5. The paper electrophoretic distribution of soluble proteins in different regions of human brain
- Author
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D. M. Robertson
- Subjects
Brain Chemistry ,Cellular and Molecular Neuroscience ,Electrophoresis ,Brain chemistry ,medicine.anatomical_structure ,Chemistry ,Biophysics ,medicine ,Distribution (pharmacology) ,Brain ,Proteins ,Human brain ,Biochemistry - Published
- 1960
6. PROTEIN INCORPORATION AND AXOPLASMIC FLOW IN MOTONEURON FIBRES FOLLOWING INTRA-CORD INJECTION OF LABELLED LEUCINE
- Author
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J. Johnson, M.‐H. Ng, and Sidney Ochs
- Subjects
Cord ,Chromatography, Paper ,Neural Conduction ,Centrifugation ,Tritium ,Biochemistry ,Injections ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Leucine ,medicine ,Animals ,Trichloroacetic Acid ,Trichloroacetic acid ,Motor Neurons ,Carbon Isotopes ,CATS ,Phosphorus Isotopes ,Proteins ,Phosphorus ,Spinal cord ,Axons ,medicine.anatomical_structure ,Spinal Cord ,chemistry ,Puromycin ,Cats ,Axoplasmic transport ,Biophysics ,Autoradiography - Published
- 1967
7. Multiple biochemical similarities between infectious and non-infectious aggregates of a prion protein carrying an octapeptide insertion.
- Author
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Biasini, Emiliano, Medrano, Andrea Z., Thellung, Stefano, Chiesa, Roberto, and Harris, David A.
- Subjects
PROTEINS ,MINERAL aggregates ,PEPTIDES ,ORGANIC compounds ,AMINO acids - Abstract
A nine-octapeptide insertion in the prion protein (PrP) gene is associated with an inherited form of human prion disease. Transgenic (Tg) mice that express the mouse homolog of this mutation (designated PG14) spontaneously accumulate in their brains an insoluble and weakly protease-resistant form of the mutant protein. This form (designated PG14
Spon ) is highly neurotoxic, but is not infectious in animal bioassays. In contrast, when Tg(PG14) mice are inoculated with the Rocky Mountain Laboratory (RML) strain of prions, they accumulate a different form of PG14 PrP (designated PG14RML ) that is highly protease resistant and infectious in animal transmission experiments. We have been interested in characterizing the molecular properties of PG14Spon and PG14RML , with a view to identifying features that determine two, apparently distinct properties of PrP aggregates: their infectivity and their pathogenicity. In this paper, we have subjected PG14Spon and PG14RML to a panel of assays commonly used to distinguish infectious PrP (PrPSc ) from cellular PrP (PrPC ), including immobilized metal affinity chromatography, precipitation with sodium phosphotungstate, and immunoprecipitation with PrPC - and PrPSc -specific antibodies. Surprisingly, we found that aggregates of PG14Spon and PG14RML behave identically to each other, and to authentic PrPSc , in each of these biochemical assays. PG14Spon however, in contrast to PG14RML and PrPSc , was unable to seed the misfolding of PrPC in an in vitro protein misfolding cyclic amplification reaction. Collectively, these results suggest that infectious and non-infectious aggregates of PrP share common structural features accounting for their toxicity, and that self-propagation of PrP involves more subtle molecular differences. [ABSTRACT FROM AUTHOR]- Published
- 2008
- Full Text
- View/download PDF
8. Neuropathology, biochemistry, and biophysics of α-synuclein aggregation.
- Author
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Uversky, Vladimir N.
- Subjects
PROTEINS ,BRAIN ,BIOCHEMISTRY ,BIOPHYSICS ,NEURODEGENERATION ,MOLECULAR structure ,PROTEIN folding - Abstract
Aggregation of α-synuclein, an abundant and conserved pre-synaptic brain protein, is implicated as a critical factor in several neurodegenerative diseases. These diseases, known as synucleinopathies, include Parkinson’s disease, dementia with Lewy bodies (LBs), diffuse LB disease, the LB variant of Alzheimer’s disease, multiple system atrophy, and neurodegeneration with brain iron accumulation type I. Although the precise nature of in vivoα-synuclein function remains elusive, considerable knowledge has been accumulated about its structural properties and conformational behavior. α-Synuclein is a typical natively unfolded protein. It is characterized by the lack of rigid, well-defined, 3-D structure and possesses remarkable conformational plasticity. The structure of this protein depends dramatically on its environment and it accommodates a number of unrelated conformations. This paper provides an overview of the biochemistry, biophysics, and neuropathology of α-synuclein aggregation. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
9. S100A1 codistributes with synapsin I in discrete brain areas and inhibits the F-actin-bundling activity of synapsin I.
- Author
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Benfenati, Fabio, Ferrari, Rosaria, Onofri, Franco, Arcuri, Cataldo, Giambanco, Ileana, and Donato, Rosario
- Subjects
CYTOSKELETON ,CYTOPLASM ,EXOCYTOSIS ,CELL physiology ,PROTEINS ,CARRIER proteins - Abstract
The Ca
2+ -sensor protein S100A1 was recently shown to bind in vitro to synapsins, a family of synaptic vesicle phosphoproteins involved in the regulation of neurotransmitter release. In this paper, we analyzed the distribution of S100A1 and synapsin I in the CNS and investigated the effects of the S100A1/synapsin binding on the synapsin functional properties. Subcellular fractionation of rat brain homogenate revealed that S100A1 is present in the soluble fraction of isolated nerve endings. Confocal laser scanning microscopy and immunogold immunocytochemistry demonstrated that S100A1 and synapsin codistribute in a subpopulation (5–20%) of nerve terminals in the mouse cerebral and cerebellar cortices. By forming heterocomplexes with either dephosphorylated or phosphorylated synapsin I, S100A1 caused a dose- and Ca2+ -dependent inhibition of synapsin-induced F-actin bundling and abolished synapsin dimerization, without affecting the binding of synapsin to F-actin, G-actin or synaptic vesicles. These data indicate that: (i) synapsins and S100A1 can interact in the nerve terminals where they are coexpresssed; (ii) S100A1 is unable to bind to SV-associated synapsin I and may function as a cytoplasmic store of monomeric synapsin I; and (iii) synapsin dimerization and interaction with S100A1 are mutually exclusive, suggesting an involvement of S100A1 in the Ca2+ -dependent regulation of synaptic vesicle trafficking. [ABSTRACT FROM AUTHOR]- Published
- 2004
- Full Text
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10. A single protective polymorphism in the prion protein blocks cross‐species prion replication in cultured cells.
- Author
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Arshad, Hamza, Patel, Zeel, Amano, Genki, Li, Le yao, Al‐Azzawi, Zaid A. M., Supattapone, Surachai, Schmitt‐Ulms, Gerold, and Watts, Joel C.
- Subjects
SCRAPIE ,SMALL molecules ,PRIONS ,MONOCLONAL antibodies ,PROTEINS ,GENETIC variation ,AMINO acids ,HAMSTERS - Abstract
The bank vole (BV) prion protein (PrP) can function as a universal acceptor of prions. However, the molecular details of BVPrP's promiscuity for replicating a diverse range of prion strains remain obscure. To develop a cultured cell paradigm capable of interrogating the unique properties of BVPrP, we generated monoclonal lines of CAD5 cells lacking endogenous PrP but stably expressing either hamster (Ha), mouse (Mo), or BVPrP (M109 or I109 polymorphic variants) and then challenged them with various strains of mouse or hamster prions. Cells expressing BVPrP were susceptible to both mouse and hamster prions, whereas cells expressing MoPrP or HaPrP could only be infected with species‐matched prions. Propagation of mouse and hamster prions in cells expressing BVPrP resulted in strain adaptation in several instances, as evidenced by alterations in conformational stability, glycosylation, susceptibility to anti‐prion small molecules, and the inability of BVPrP‐adapted mouse prion strains to infect cells expressing MoPrP. Interestingly, cells expressing BVPrP containing the G127V prion gene variant, identified in individuals resistant to kuru, were unable to become infected with prions. Moreover, the G127V polymorphic variant impeded the spontaneous aggregation of recombinant BVPrP. These results demonstrate that BVPrP can facilitate cross‐species prion replication in cultured cells and that a single amino acid change can override the prion‐permissive nature of BVPrP. This cellular paradigm will be useful for dissecting the molecular features of BVPrP that allow it to function as a universal prion acceptor. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
11. A human blood–arachnoid barrier atlas of transporters, receptors, enzymes, and tight junction and marker proteins: Comparison with dog and pig in absolute abundance.
- Author
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Uchida, Yasuo, Takeuchi, Hina, Goto, Ryohei, Braun, Clemens, Fuchs, Holger, Ishiguro, Naoki, Takao, Masaki, Tano, Mitsutoshi, and Terasaki, Tetsuya
- Subjects
FEMALE dogs ,TIGHT junctions ,SWINE ,ENZYMES ,PROTEIN expression ,PROTEINS - Abstract
The purpose of this study was to elucidate the absolute abundance of transporters, enzymes, receptors, and tight junction and marker proteins at human blood–arachnoid barrier (BAB) and compare with those of dogs and pigs. Protein expression levels in plasma membrane fractions of brain leptomeninges were determined by quantitative targeted absolute proteomics. To realistically compare the absolute abundance of target molecules at the BAB among humans, dogs, and pigs, the unit was converted from fmol/μg‐protein to pmol/cm2‐leptomeninges. Of a total of 70 proteins, 52 were detected. OAT1, OAT3, GLUT1, 4F2hc, EAAT1, EAAT2, MCT8, SMVT, CTL2, GFAP, Claudin‐5, Na+/K+‐ATPase, COMT, GSTP1, and CES1 were abundantly expressed at the human BAB (>1 pmol/cm2). The protein expression levels were within a 3‐fold difference for 16 out of 33 proteins between humans and dogs and for 13 out of 28 proteins between humans and pigs. Both human–dog and human–pig differences in protein expression levels were within 3‐fold for OAT1, OAT3, 4F2hc, xCT, OCT2, MDR1, BCRP, PEPT2, SYP, and MCT1. In contrast, OCT3, MCT4, and OATP1A2 were detected in humans but not in dogs or pigs. MRP3 was detected in dogs and pigs but not in humans. The absolute level of GLUT1 in humans was nearly the same as that in dogs but was 6.14‐fold greater in pigs. No significant differences in the levels were observed between male and female dogs for nearly all molecules. These results should be helpful in understanding the physiological roles of BAB and cerebrospinal fluid pharmacokinetics in humans and their differences from dogs and pigs. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
12. Cellular Fate: Proliferation, Survival, Differentiation Processes.
- Subjects
- *
NEURONS , *PROTEINS , *BRAIN , *CELL differentiation - Abstract
Presents abstracts of papers featured in the "Journal of Neurochemistry" that deal with proliferation, survival and differentiation processes in cells. "Influence of prenatal irradiation by 131-I on the heparin-binding activity of newborn rat brain proteins"; Cannabinoid inhibition of neuronal differentiation".
- Published
- 2003
- Full Text
- View/download PDF
13. Poster Session AP10: Astrocytes.
- Subjects
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ASTROCYTES , *MITOCHONDRIAL membranes , *GLUTATHIONE , *PROTEINS , *POSTER presentations - Abstract
The article presents abstracts of papers related to astrocytes, which were presented at a poster session at the meeting of the International Society for Neurochemistry and the American Society for Neurochemistry, held in Buenos Aires, Argentina from August 26-31, 2001. The abstracts include "Mitochondrial function and glutathione status in astrocytes," "A study of rat astroglial cells after the administration of a convulsant drug," and "Synaptic proteins in astrocytes."
- Published
- 2001
14. Three‐finger proteins from snakes and humans acting on nicotinic receptors: Old and new.
- Author
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Tsetlin, Victor I., Kasheverov, Igor E., and Utkin, Yuri N.
- Subjects
NICOTINIC acetylcholine receptors ,MUSCARINIC acetylcholine receptors ,SNAKE venom ,NICOTINIC receptors ,PROTEINS ,BINDING sites ,SNAKES - Abstract
The first toxin to give rise to the three‐finger protein (TFP) family was α‐bungarotoxin (α‐Bgt) from Bungarus multicinctus krait venom. α‐Bgt was crucial for research on nicotinic acetylcholine receptors (nAChRs), and in this Review article we focus on present data for snake venom TFPs and those of the Ly6/uPAR family from mammalians (membrane‐bound Lynx1 and secreted SLURP‐1) interacting with nAChRs. Recently isolated from Bungarus candidus venom, αδ‐bungarotoxins differ from α‐Bgt: they bind more reversibly and distinguish two binding sites in Torpedo californica nAChR. Naja kaouthia α‐cobratoxin, classical blocker of nAChRs, was shown to inhibit certain GABA‐A receptor subtypes, whereas α‐cobratoxin dimer with 2 intermolecular disulfides has a novel type of 3D structure. Non‐conventional toxin WTX has additional 5th disulfide not in the central loop, as α‐Bgt, but in the N‐terminal loop, like all Ly6/uPAR proteins, and inhibits α7 and Torpedo nAChRs. A water‐soluble form of Lynx1, ws‐Lynx1, was expressed in E. coli, its 1H‐NMR structure and binding to several nAChRs determined. For SLURP‐1, similar information was obtained with its recombinant analogue rSLURP‐1. A common feature of ws‐Lynx1, rSLURP‐1, and WTX is their activity against nAChRs and muscarinic acetylcholine receptors. Synthetic SLURP‐1, identical to the natural protein, demonstrated some differences from rSLURP‐1 in distinguishing nAChR subtypes. The loop II fragment of the Lynx1 was synthesized having the same µM affinity for the Torpedo nAChR as ws‐Lynx1. This review illustrates the productivity of parallel research of nAChR interactions with the two TFP groups. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
15. Phosphorylation‐dependent control of Activity‐regulated cytoskeleton‐associated protein (Arc) protein by TNIK.
- Author
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Walczyk‐Mooradally, Alicyia, Holborn, Jennifer, Singh, Karamjeet, Tyler, Marshall, Patnaik, Debasis, Wesseling, Hendrik, Brandon, Nicholas J., Steen, Judith, Graether, Steffen P., Haggarty, Stephen J., and Lalonde, Jasmin
- Subjects
GAG proteins ,POST-translational modification ,COGNITIVE ability ,SITE-specific mutagenesis ,PROTEINS ,CAPSIDS - Abstract
Activity‐regulated cytoskeleton‐associated protein (Arc) is an immediate early gene product that support neuroplastic changes important for cognitive function and memory formation. As a protein with homology to the retroviral Gag protein, a particular characteristic of Arc is its capacity to self‐assemble into virus‐like capsids that can package mRNAs and transfer those transcripts to other cells. Although a lot has been uncovered about the contributions of Arc to neuron biology and behavior, very little is known about how different functions of Arc are coordinately regulated both temporally and spatially in neurons. The answer to this question we hypothesized must involve the occurrence of different protein post‐translational modifications acting to confer specificity. In this study, we used mass spectrometry and sequence prediction strategies to map novel Arc phosphorylation sites. Our approach led us to recognize serine 67 (S67) and threonine 278 (T278) as residues that can be modified by TNIK, which is a kinase abundantly expressed in neurons that shares many functional overlaps with Arc and has, along with its interacting proteins such as the NMDA receptor, and been implicated as a risk factor for psychiatric disorders. Furthermore, characterization of each residue using site‐directed mutagenesis to create S67 and T278 mutant variants revealed that TNIK action at those amino acids can strongly influence Arc's subcellular distribution and self‐assembly as capsids. Together, our findings reveal an unsuspected connection between Arc and TNIK. Better understanding of the interplay between these two proteins in neuronal cells could lead to new insights about apparition and progression of psychiatric disorders. Cover Image for this issue: https://doi.org/10.1111/jnc.15077 [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
16. Cerebrospinal fluid and serum protein markers in autism: A co‐twin study.
- Author
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Smedler, Erik, Kleppe, Johanna, Neufeld, Janina, Lundin, Karl, Bölte, Sven, and Landén, Mikael
- Subjects
BLOOD proteins ,TALL-1 (Protein) ,AUTISM spectrum disorders ,BIOMARKERS ,CEREBROSPINAL fluid ,AUTISM - Abstract
No robust biomarkers have yet been identified for autism spectrum disorder (ASD) or autistic traits. Familial factors likely influence biomarkers such as protein concentrations. Comparing twins with ASD or high autistic traits to the less affected co‐twin allows estimating the impact of familial confounding. We measured 203 proteins in cerebrospinal fluid (n = 86) and serum (n = 127) in twins (mean age 14.2 years, 44.9% females) enriched for ASD and other neurodevelopmental conditions. Autistic traits were assessed by using the parent‐report version of the Social Responsiveness Scale‐2. In cerebrospinal fluid, autistic traits correlated negatively with three proteins and positively with one. In serum, autistic traits correlated positively with 15 and negatively with one. Also in serum, six were positively—and one negatively—associated with ASD. A pathway analysis of these proteins revealed immune system enrichment. In within twin pair analyses, autistic traits were associated with serum B‐cell activating factor (BAFF) only, whereas Cystatin B (CSTB) remained significantly associated with ASD. These associations did not remain significant when only considering monozygotic twins. For the remainder, the within‐pair analysis indicated familial confounding, including shared environment and genes, influencing both autism and protein levels. Our findings indicate proteins involved in immunity as putative biomarkers of autistic traits and ASD with partial genetic confounding. Although some results are in line with previous studies in general, further studies are needed for replication. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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17. SUMOylation of synaptic and synapse‐associated proteins: An update.
- Author
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Henley, Jeremy M., Seager, Richard, Nakamura, Yasuko, Talandyte, Karolina, Nair, Jithin, and Wilkinson, Kevin A.
- Subjects
SYNAPSES ,SMALL ubiquitin-related modifier proteins ,POST-translational modification ,NUCLEAR proteins ,PROTEINS ,NEUROPLASTICITY ,NEURAL transmission - Abstract
SUMOylation is a post‐translational modification that regulates protein signalling and complex formation by adjusting the conformation or protein–protein interactions of the substrate protein. There is a compelling and rapidly expanding body of evidence that, in addition to SUMOylation of nuclear proteins, SUMOylation of extranuclear proteins contributes to the control of neuronal development, neuronal stress responses and synaptic transmission and plasticity. In this brief review we provide an update of recent developments in the identification of synaptic and synapse‐associated SUMO target proteins and discuss the cell biological and functional implications of these discoveries. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
18. The uptake of tau amyloid fibrils is facilitated by the cellular prion protein and hampers prion propagation in cultured cells.
- Author
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De Cecco, Elena, Celauro, Luigi, Vanni, Silvia, Grandolfo, Micaela, Bistaffa, Edoardo, Moda, Fabio, Aguzzi, Adriano, and Legname, Giuseppe
- Subjects
PRIONS ,TAU proteins ,AMYLOID ,PROTEINS ,BRAIN diseases ,CELLS - Abstract
Tauopathies are prevalent, invariably fatal brain diseases for which no cure is available. Tauopathies progressively affect the brain through cell‐to‐cell transfer of tau protein amyloids, yet the spreading mechanisms remain unknown. Here we show that the cellular prion protein (PrPC) facilitates the uptake of tau aggregates by cultured cells, possibly by acting as an endocytic receptor. In mouse neuroblastoma cells, pull‐down experiments revealed that tau amyloids bind to PrPC. Confocal images of both wild‐type and PrPC ‐knockout N2a cells treated with fluorescently labeled synthetic tau fibrils showed that the internalization was reduced in isogenic cells devoid of the gene encoding PrPC. Pre‐treatment of the same cells with antibodies against N‐proximal epitopes of PrPC impaired the binding of tau amyloids and decreased their uptake. Surprisingly, exposure of chronically prion‐infected cells to tau amyloids reduced the accumulation of aggregated prion protein and this effect lasted for more than 72 hr after amyloid removal. These results point to bidirectional interactions between the two proteins: while PrPC mediates the entrance of tau fibrils in cells, PrPSc buildup is greatly reduced in their presence, possibly because of an impairment in the prion conversion process. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
19. Poster Session AP16: Axonal growth and transport.
- Subjects
- *
AXONAL transport , *PRESYNAPTIC receptors , *PHOSPHOINOSITIDES , *PROTEINS - Abstract
The article presents abstracts of papers related to axonal growth and transport. They include "Intravitreal endothelin-1 significantly alters the temporal characteristics and the protein profiles of anterograde fast axonal transport in rat optic nerve," "Targeting of the presynaptic cytomatrix protein bassoon to the active zone," and "The inhibition of phosphatidylinositol 3-kinase induces neurite retraction and activates GSK3."
- Published
- 2001
20. PHOSPHORYLATION OF INITIATION FACTOR 4E AND ITS ASSOCIATED PROTEINS DURING ISCHEMIA.
- Author
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Martin, Maria Elena, Muñoz, Francisco M., Salinas, Matilde, and Fando, Juan L.
- Subjects
- *
PHOSPHORYLATION , *ISCHEMIA , *PROTEINS , *REPERFUSION , *MEDICAL research - Abstract
The article presents an abstract of the medical research paper "Phosphorylation of Initiation Factors 4E and Its Associated Proteins During Ischemia." This paper is to be discussed in the Seventeenth Biennial Meeting of the International Society for Neurochemistry (ISN) and the Thirteenth General Meeting of the European Society for Neurochemistry (ESN) to be held at Berlin, Germany from August 8-14, 1999.
- Published
- 1999
21. CHARACTERIZATION OF FUNCTIONAL DOMAINS OF THE DROSOPHILA TUMOR SUPPRESSOR AND SYNAPSE PROTEIN DLG.
- Author
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Ebitsch, S., Thomas, U., Gorczyca, M., Budnik, V., and Gundelfinger, E. D.
- Subjects
- *
NEUROCHEMISTRY , *DROSOPHILIDAE , *SYNAPSES , *TUMOR suppressor genes , *PROTEINS - Abstract
The article presents an abstract of the research paper "Characterization of Functional Domains of the Drosophila Tumor Suppressor and Synapse protein DLG." Analysis of dlg mutants asserted the involvement DLG in the maintenance of epithelial junctions and glutamatergic synapses. The research paper brought out the dissimilarity between the requirements of epithelial junctions and neuromuscular junction.
- Published
- 1999
22. GLYCOLIPID-DEPENDENCE ON THE MOLECULAR COMPOSITION OF DETERGENT-INSOLUBLE GLYCOSPHINGOLIPID-CHOLESTEROL ENRICHED MICRODOMAINS IN MICE LACKING GALACTOCEREBROSIDE AND SULFATIDE.
- Author
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Kim, T., Bansal, R., and Pfeiffer, S. E.
- Subjects
- *
NEUROCHEMISTRY , *GLYCOSPHINGOLIPIDS , *MICE , *PROTEINS , *MYELIN proteins - Abstract
The article presents an abstract of the research paper of "Glycolipid-Dependence on the Molecular Composition of Detergent-Insoluble Glycosphingolipid-Cholesterol Enriched Microdomains in Mice Lacking Galactocerebroside and Sulfatide." The paper investigates changes in the pattern of proteins involved with DIGCEMs from myelin lacking the major myelin glycolipids galactocerebroside and sulfatide.
- Published
- 1999
23. FUNCTIONAL REGULATION OF GABA TRANSPORTERS.
- Author
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Quick, Michael W., Bernstein, Eve, and Beckman, Matthew L.
- Subjects
- *
GABA , *NEUROCHEMISTRY , *PROTEINS , *HIPPOCAMPUS (Brain) - Abstract
The article presents an abstract of the research paper "Functional Regulation of GABA Transporters." It will be presented in the joint meeting of the International Society for Neurochemistry and the European Society for Neurochemistry that will be held in Berlin, Germany from August 8-14, 1999. The paper examines the roles of second messengers and SNARE proteins in the regulation of GABA transporter in neuronal cultures from rat hippocampus.
- Published
- 1999
24. MOLECULAR MECHANISMS OF NEUROTRANSMITI'ER RELEASE.
- Author
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Augustine, George J.
- Subjects
- *
NEUROTRANSMITTERS , *NEUROCHEMISTRY , *SYNAPSES , *PROTEINS - Abstract
The article presents an abstract of the research paper "Molecular Mechanisms of Neurotransmitter Release." It will be presented in the joint meeting of the International Society for Neurochemistry and the European Society for Neurochemistry that will be held in Berlin, Germany from August 8-14, 1999. The paper evaluates the potential roles of a number of presynaptic proteins in the release of neurotransmitter with the help of squid giant synapse.
- Published
- 1999
25. SNARE COMPLEX FORMATION IS TRIGGERED BY CA2+ AND DRIVES MEMBRANE FUSION.
- Author
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Scheller, Richard H.
- Subjects
- *
MEMBRANE fusion , *NEUROCHEMISTRY , *CALCIUM ions , *PROTEINS - Abstract
The article presents an abstract of the research paper "SNARE Complex Formation is Triggered by Ca2+ and Drives Membrane Fusion." It will be presented in the joint meeting of the International Society for Neurochemistry and the European Society for Neurochemistry that will be held in Berlin, Germany from August 8-14, 1999. The paper proves that the pairing of SNARE proteins on opposing membranes leads to bilayer fusion and results in a high affinity cis-SNARE complex.
- Published
- 1999
26. FORMATION OF ADVANCED GLYCATION END PRODUCTS BY HUMAN PROTEOLIPID PROTEIN.
- Author
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Li, L., De Sa, P., Koul, O., Lees, M. B., and Dain, J. A.
- Subjects
- *
PROTEINS , *CENTRAL nervous system , *PATHOLOGICAL physiology , *DIABETES , *CONFERENCES & conventions , *ASSOCIATIONS, institutions, etc. - Abstract
The article presents an abstract of the paper "Formation of Advanced Glycation End Products by Human Proteolipid Protein," which will be presented at the 30th Annual Meeting of the American Society for Neurochemistry to be held from March 14-17, 1999 in New Orleans, Louisiana. Proteolipid was found to be a target protein for glycation and advanced glycation end products formation in the brain in the paper and it can be engaged in the central nervous system pathophysiology in diabetes.
- Published
- 1999
27. ACTIVITY-DEPENDENT NEUROPROTECTIVE PROTEIN: MOLECULAR STRUCTURE AND BEHAVIORAL STUDIES.
- Author
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Gozes, Illana, Zamostiano, Rachel, Giladi, Eliezer, Pinhasov, Albert, Bassan, Merav, and Brenneman, Douglas E.
- Subjects
- *
AMINO acid sequence , *PROTEINS , *MOLECULAR structure , *ASSOCIATIONS, institutions, etc. , *PEPTIDES - Abstract
The article presents an abstract of the paper "Activity-Dependent Neuroprotective Protein: Molecular Structure and Behavioral Studies," which will be presented at the 30th annual meeting of the American Society for Neurochemistry to be held from March 14-17, 1999 in New Orleans, Louisiana. The paper discusses the coding sequence of the activity-dependent neuroprotective protein. It contained glycosilation domains, zinc-binding fingers, a glutaredoxin active site and a putative signal peptide.
- Published
- 1999
28. Workshop W01: PLP and PLP Mutants - What's New?
- Author
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Knapp, P.
- Subjects
- *
LIPIDS , *PROTEINS , *GENETIC mutation , *NEUROLOGY , *INTRONS , *MYELIN sheath , *NEURAL development , *DEVELOPMENTAL neurobiology - Abstract
The article presents abstracts of research papers about proteolipid protein (Plp) and Plp mutants in neurology. They include "Targeted deletion of the antisilencer/enhancer regulatory element from intron 1 of the mouse myelin Plp gene," and "Is PLP necessary for brain development and function? the human perspective'."
- Published
- 2006
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29. Selective up-regulation of functional mu-opioid receptor splice variants by chronic opioids.
- Author
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Chakrabarti, Sumita, Madia, Priyanka A., and Gintzler, Alan R.
- Subjects
OPIOID receptors ,SPLICEOSOMES ,GENETIC code ,MESSENGER RNA ,PROTEINS - Abstract
We recently reported (Verzillo, et al. J. Neurochem: 130, 790-796, 2014) that chronic systemic morphine selectively up-regulates mRNA encoding two C-terminal μ-opioid receptor (MOR) splice variants, MOR-1C1 and MOR-1B2 (MOR-1B2/-1C1). Given the known disconnects between changes in levels of mRNA and corresponding protein, it is essential to directly demonstrate that chronic opioid treatment elevates functional MOR-1B2/-1C1 protein prior to inferring relevance of these MOR variants to spinal opioid tolerance mechanisms. Accordingly, we investigated the ability of chronic opioid exposure to up-regulate MOR protein in Chinese hamster ovary cells stably transfected with rat MOR variants MOR-1B2, MOR-1C1, or MOR-1 (considered to be the predominant MOR). Findings revealed that chronic treatment with the clinically relevant opioids morphine, oxycodone and hydrocodone substantially up-regulated membrane MOR-1B2/-1C1 protein. This up-regulation was abolished by the protein synthesis inhibitor cycloheximide, eliminating contributions from receptor redistribution. The increment in MOR-1B2/-1C1 protein was paralleled by a significant increment in opioid agonist-stimulated GTPγS-binding (reflective of increased aggregate MOR G protein coupling) indicating that up-regulated MOR-1B2/-1C1 represented functional receptors. Strikingly, these tolerance-associated adaptations of MOR-1B2/-1C1 differed considerably from those of MOR-1. Antithetical regulation of MOR-1B2/-1C1 and MOR-1 by chronic opioids has significant implications for the design of new therapeutic agents to counteract opioid analgesic tolerance and accompanying addiction. Since chronic opioids induce MOR-1B2/-1C1 up-regulation in spinal cord of males, but not females, elucidating cellular compartments and intracellular pathways mediating MOR-1B2/-1C1 up-regulation and defining their unique signaling attributes would enable a precision medicinal approach to pain management and addiction therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
30. Poster Session BP17: Ion channels.
- Subjects
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ION channels , *COBRA venom factor , *CELL lines , *PROTEINS , *CALCIUM channels - Abstract
The article presents abstracts of research papers related to ion channels. They include "Cobra venom contains protein of CRISP family," "Changes in calcium channel expression upon differentiation in the cholinergic cell line SN56," and "Carnosine, a brain dipeptide selectively blocks copper but not zinc modulation in P2X-ATP receptors."
- Published
- 2001
31. Protein misfolding cyclic amplification induces the conversion of recombinant prion protein to PrP oligomers causing neuronal apoptosis.
- Author
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Yuan, Zhen, Yang, Lifeng, Chen, Baian, Zhu, Ting, Hassan, Mohammad Farooque, Yin, Xiaomin, Zhou, Xiangmei, and Zhao, Deming
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PROTEINS ,OLIGOMERS ,MONOMERS ,ANTINEOPLASTIC agents ,APOPTOSIS - Abstract
The formation of neurotoxic prion protein (PrP) oligomers is thought to be a key step in the development of prion diseases. Recently, it was determined that the sonication and shaking of recombinant PrP can convert PrP monomers into β-state oligomers. Herein, we demonstrate that β-state oligomeric PrP can be generated through protein misfolding cyclic amplification from recombinant full-length hamster, human, rabbit, and mutated rabbit PrP, and that these oligomers can be used for subsequent research into the mechanisms of PrP-induced neurotoxicity. We have characterized protein misfolding cyclic amplification-induced monomer-to-oligomer conversion of PrP from three species using western blotting, circular dichroism, size-exclusion chromatography, and resistance to proteinase K (PK) digestion. We have further shown that all of the resulting β-oligomers are toxic to primary mouse cortical neurons independent of the presence of PrP
C in the neurons, whereas the corresponding monomeric PrP were not toxic. In addition, we found that this toxicity is the result of oligomer-induced apoptosis via regulation of Bcl-2, Bax, and caspase-3 in both wild-type and PrP−/− cortical neurons. It is our hope that these results may contribute to our understanding of prion transformation within the brain. [ABSTRACT FROM AUTHOR]- Published
- 2015
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32. Mechanisms of neuroprotection by hemopexin: modeling the control of heme and iron homeostasis in brain neurons in inflammatory states.
- Author
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Hahl, Peter, Davis, Taron, Washburn, Cecilia, Rogers, Jack T., and Smith, Ann
- Subjects
HEMOPEXIN ,BRAIN research ,STROKE ,HEMORRHAGE ,NEURONS ,PROTEINS - Abstract
Hemopexin provides neuroprotection in mouse models of stroke and intracerebral hemorrhage and protects neurons in vitro against heme or reactive oxygen species (ROS) toxicity via heme oxygenase-1 (HO1) activity. To model human brain neurons experiencing hemorrhages and inflammation, we used human neuroblastoma cells, heme-hemopexin complexes, and physiologically relevant ROS, for example, H
2 O2 and HOCl, to provide novel insights into the underlying mechanism whereby hemopexin safely maintains heme and iron homeostasis. Human amyloid precursor protein ( hAPP), needed for iron export from neurons, is induced ~twofold after heme-hemopexin endocytosis by iron from heme catabolism via the iron-regulatory element of hAPP mRNA. Heme-hemopexin is relatively resistant to damage by ROS and retains its ability to induce the cytoprotective HO1 after exposure to tert-butylhydroperoxide, although induction is impaired, but not eliminated, by exposure to high concentrations of H2 O2 in vitro. Apo-hemopexin, which predominates in non-hemolytic states, resists damage by H2 O2 and HOCl, except for the highest concentrations likely in vivo. Heme-albumin and albumin are preferential targets for ROS; thus, albumin protects hemopexin in biological fluids like CSF and plasma where it is abundant. These observations provide strong evidence that hemopexin will be neuroprotective after traumatic brain injury, with heme release in the CNS, and during the ensuing inflammation. Hemopexin sequesters heme, thus preventing unregulated heme uptake that leads to toxicity; it safely delivers heme to neuronal cells; and it activates the induction of proteins including HO1 and hAPP that keep heme and iron at safe levels in neurons. [ABSTRACT FROM AUTHOR]- Published
- 2013
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33. Resistance to trophic neurite outgrowth of sensory neurons exposed to insulin.
- Author
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Singh, Bhagat, Xu, Yongqin, McLaughlin, Todd, Singh, Vandana, Martinez, Jose A., Krishnan, Anand, and Zochodne, Douglas W.
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SENSORY neurons ,INSULIN ,PROTEINS ,MESSENGER RNA ,DIABETES - Abstract
J. Neurochem. (2012) 121, 263-276. Abstract Insulin offers trophic support through receptors expressed widely on peripheral neurons. In this work, we studied whether peripheral sensory neurons demonstrate resistance to its trophic properties, a property relevant during type 2 diabetes mellitus or following supraphysiological therapy. Insulin receptors were not only localized to neuronal membranes and cytoplasm but also had a unique, previously unrecognized localization to neuronal nuclei. We confirmed that nanomolar doses increased neurite outgrowth of adult sensory neurons, but in response to micromolar doses of insulin, even following a brief 2-h exposure, survival and outgrowth of neurites were blunted. Neurons exposed to picomolar insulin concentrations in their media for 5 days had resistance to the impact of later nanomolar doses of insulin. Using a stripe assay seeded with insulin, neurites were more likely to reject higher doses of insulin. Insulin down-regulated mRNAs of the insulin receptor β subunit and up-regulated levels of GSK-3β, both potential mechanisms of insulin resistance, while down-regulating the protein expression of pAkt and pGSK-3β. Overall, these studies identify neuronal nuclear targeting of insulin and evidence for insulin-induced resistance to its trophic properties. The findings have implications for the understanding of the actions of insulin in the treatment of diabetes and neurological disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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34. Dendrimer-mediated siRNA delivery knocks down Beclin 1 and potentiates NMDA-mediated toxicity in rat cortical neurons.
- Author
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Pérez-Carrión, María D., Pérez-Martínez, Francisco C., Merino, Sonia, Sánchez-Verdú, Prado, Martínez-Hernández, José, Luján, Rafael, and Ceña, Valentín
- Subjects
HOMEOSTASIS ,LYSOSOMES ,CYTOPLASMIC granules ,RNA ,NEURONS ,PROTEINS - Abstract
J. Neurochem. (2012) 120, 259-268. Abstract Autophagy is an important process which plays a key role in cellular homeostasis by degrading cytoplasmic components in the lysosomes, which facilitates recycling. Alterations to normal autophagy have been linked to excitotoxicity, but the mechanisms governing its signal transduction remain unclear. The aim of this study was to explore the role of autophagy in neuronal excitotoxic death by delivering small interfering RNA (siRNA) to rat cortical neurons, using a dendrimer to silence the autophagy-related gene 6 (beclin 1) and to determine the role of autophagy in excitotoxicity. We have found that the dendrimer is very efficient to deliver siRNA to rat cortical neurons, leading to almost complete removal of the target protein Beclin 1. In addition, NMDA increases autophagy markers, such as the protein levels of Beclin 1, the microtubule-associated light chain 3 (LC3) B-II/LC3B-I ratio, and monodansylcadaverine (MDC) labeling in rat cortical neurons. Moreover, NMDA also increases the formation of autophagosomes observed under a transmission electron microscope. Silencing beclin 1 expression blocked NMDA-induced autophagy. Moreover, Beclin 1 removal potentiated NMDA-induced neuronal death indicating that autophagy plays a protective role during excitotoxicity and suggesting that targeting autophagy might be a helpful therapeutic strategy in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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35. Between promiscuity and specificity: novel roles of EF-hand calcium sensors in neuronal Ca2+ signalling.
- Author
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Mikhaylova, Marina, Hradsky, Johannes, and Kreutz, Michael R.
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CALMODULIN ,CALCIUM ,NEURONS ,PROTEINS ,MATERIAL plasticity - Abstract
J. Neurochem. (2011) 118, 695-713. Abstract In recent years, substantial progress has been made towards an understanding of the physiological function of EF-hand calcium sensor proteins of the Calmodulin (CaM) superfamily in neurons. This deeper appreciation is based on the identification of novel target interactions, structural studies and the discovery of novel signalling mechanisms in protein trafficking and synaptic plasticity, in which CaM-like sensor proteins appear to play a role. However, not all interactions are of plausible physiological relevance and in many cases it is not yet clear how the CaM signaling network relates to the proposed function of other EF-hand sensors. In this review, we will summarize these findings and address some of the open questions on the functional role of EF-hand calcium binding proteins in neurons. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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36. Altered expression of key dopaminergic regulatory proteins in the postnatal brain following perinatal n-3 fatty acid dietary deficiency.
- Author
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Kuperstein, Faina, Eilam, Raya, and Yavin, Ephrain
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PROTEINS ,LINOLENIC acids ,DOPAMINE ,FATTY acids ,BRAIN ,ENZYMES ,MICROGLIA - Abstract
The consequences of maternal linolenic acid (LNA, 18:3n-3) dietary deficiency on key dopamine (DA)-associated regulatory proteins in mesolimbic and mesocortical structures of the postnatal rat brain have been investigated. A marked (4.5-fold) decrease of the DA-synthesizing enzyme tyrosine hydroxylase accompanied by a down-regulation (approx 7.5-fold) of the vesicular monoamine transporter (VMAT-2) and a depletion of VMAT-associated vesicles in the hippocampus were observed in deficient offspring compared with adequately fed controls. The DA transporter (DAT) was not affected by the LNA deficiency indicative of a DAT/VMAT-2 ratio increase that may enhance the risk of damage of the dopaminergic (DAergic) terminal. A robust increase in DA receptor (DAR1 and DAR2) levels was noticed in the cortex and striatum structures possibly to compensate for the low levels of DA in synaptic clefts. Microglia activation characterized by enhanced levels of ED1 antibody and nuclear internalization of p65 NFκB was noticed following LNA deficiency. Diminished levels of 22:6n-3 docosahexaenoic acid ( Schiefermeier and Yavin 2002 ), the most ubiquitous metabolite generated by LNA is proposed to reduce the anti-oxidant arsenal in the developing brain and cause microglia activation and enhanced oxidative stress to increase the risk of certain DA-associated neurological disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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- View/download PDF
37. Identification of multiple post-translational modifications in the porcine brain specific p25α.
- Author
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Kleinnijenhuis, Anne J., Hedegaard, Claus, Lundvig, Ditte, Sundbye, Sabrina, Issinger, Olaf Georg, Jensen, Ole Nørregaard, and Jensen, Poul Henning
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BRAIN ,PROTEINS ,LEWY body dementia ,NEURONS ,MASS spectrometry ,AMINO acids - Abstract
P25α is a protein normally expressed in oligodendrocytes and subcellular relocalization of p25α occurs in multiple system atrophy, Parkinson’s disease and Lewy body dementia along with ectopic expression in neurons. Moreover, it accumulates in Lewy body inclusions with aggregated α-synuclein and is a potent stimulator of α-synuclein aggregation. P25α is a phosphoprotein and post-translational modifications (PTMs) may play a role in its disease-related abnormalities. To investigate the spectrum of PTMs on p25α we cloned porcine p25α and isolated the protein from porcine brain. Using several complementary tandem mass spectrometry techniques for peptide mass analysis and amino acid sequencing, a comprehensive analysis of the PTMs on porcine p25α was performed. It was found that porcine p25α is heavily modified with a variety of modifications: phosphorylation, di- and trimethylation, citrullination and a HexNAc group. The modifications are localized within p25α’s unfolded terminal domains and suggest that their functional states are regulated. This comprehensive mapping of p25α’s PTMs will form the basis for future functional studies and investigations of p25α’s potential role as a biomarker. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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- View/download PDF
38. Expression of the neurosecretory process in pc12 cells is governed by rest.
- Author
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D’Alessandro, Rosalba, Klajn, Andrijana, Stucchi, Laura, Podini, Paola, Malosio, Maria Luisa, and Meldolesi, Jacopo
- Subjects
NEUROSECRETION ,CELLS ,TRANSCRIPTION factors ,PROTEINS ,EXOCYTOSIS ,CHROMOGRANINS ,STATINS (Cardiovascular agents) ,HISTONE deacetylase - Abstract
The neurosecretory process is acquired during differentiation and can be lost en block by differentiated cells. To investigate the role of REST/NRSF, a transcription repressor, in the maintenance of the process we studied two PC12 clones, one wt and one defective, expressing low and high levels of endogenous RE-1 silencing transcription (factor) (REST), respectively. Stable transfection of constructs demonstrated that REST represses 10 genes coding for proteins of neurosecretory vesicles and their exocytosis, eight including and two lacking the REST-binding sequence, RE-1. Of these genes, those of chromogranins were strongly repressed by fewfold increases of REST, those of VAMP2 and syntaxin1a required much higher levels. Moreover, in wt cells transfected with an active construct the dense-core vesicles, still competent for regulated exocytosis, were much smaller, with lighter cores; in defective cells, the dominant-negative construct induced the rescue of many vesicle/exocytosis genes but not of those of chromogranins. Small dense-core vesicles, exocytized upon stimulation, were rescued when the construct-transfected defective cells were transfected also with chromograninA or treated with trichostatinA, a blocker of histone deacetylases. Our results identify REST, working by direct and indirect mechanisms, as the factor governing the maintenance of the neurosecretory process and the properties of dense-core vesicles in PC12 cells. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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- View/download PDF
39. Differential interaction of NMDA receptor subtypes with the post-synaptic density-95 family of membrane associated guanylate kinase proteins.
- Author
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Cousins, Sarah L., Papadakis, Michalis, Rutter, A. Richard, and Stephenson, F. Anne
- Subjects
METHYL aspartate ,SYNAPSES ,PROTEINS ,GLUTAMIC acid ,VALINE - Abstract
NMDA receptors are a subclass of ionotropic glutamate receptors. They are trafficked and/or clustered at synapses by the post-synaptic density (PSD)-95 membrane associated guanylate kinase (MAGUK) family of scaffolding proteins that associate with NMDA receptor NR2 subunits via their C-terminal glutamate serine (aspartate/glutamate) valine motifs. We have carried out a systematic study investigating in a heterologous expression system, the association of the four major NMDA receptor subtypes with the PSD-95 family of MAGUK proteins, chapsyn-110, PSD-95, synapse associated protein (SAP) 97 and SAP102. We report that although each PSD-95 MAGUK was shown to co-immunoprecipitate with NR1/NR2A, NR1/NR2B, NR1/NR2C and NR1/NR2D receptor subtypes, they elicited differential effects with regard to the enhancement of total NR2 subunit expression which then results in an increased cell surface expression of NMDA receptor subtypes. PSD-95 and chapsyn-110 enhanced NR2A and NR2B total expression which resulted in increased NR1/NR2A and NR1/NR2B receptor cell surface expression whereas SAP97 and SAP102 had no effect on total or cell surface expression of these subtypes. PSD-95, chapsyn-110, SAP97 and SAP102 had no effect on either total NR2C and NR2D subunit expression or cell surface NR1/NR2C and NR1/NR2D expression. A comparison of PSD-95α, PSD-95β and PSD-95α
C3S,C5S showed that PSD-95-enhanced cell surface expression of NR1/NR2A receptors was dependent upon the PSD-95 N-terminal C3,C5 cysteines. These observations support differential interaction of NMDA receptor subtypes with different PSD-95 MAGUK scaffolding proteins. This has implications for the stabilisation, turnover and compartmentalisation of NMDA receptor subtypes in neurones during development and in the mature brain. [ABSTRACT FROM AUTHOR]- Published
- 2008
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40. Synaptogenesis and Synaptic Plasticity.
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- *
SYNAPSES , *DEVELOPMENTAL neurobiology , *PROTEINS - Abstract
Presents abstracts of papers featured in the "Journal of Neurochemistry" that deal with synaptogenesis and synaptic plasticity. "Involvement of synaptic proteins in neuronal transport"; "Protein interactions and the trafficking of AMPA receptors".
- Published
- 2003
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41. Mortality, oxidative stress and tau accumulation during ageing in parkin null mice.
- Author
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Rodríguez-Navarro, Jose A., Casarejos, M. Jos, Menéndez, Jaime, Solano, Rosa M., Rodal, Izaskun, Gómez, Ana, Yébenes, Justo García de, and Mena, Maria A.
- Subjects
AGING ,BRAIN ,NEURONS ,OXIDATIVE stress ,PROTEINS ,PARKINSON'S disease ,NEURAL transmission - Abstract
Young parkin null (pk−/−) mice have subtle abnormalities of behaviour, dopamine (DA) neurotransmission and free radical production, but no massive loss of DA neurons. We investigated whether these findings are maintained while ageing. Pk−/− mice have reduced life span and age-related reduced exploratory behaviour, abnormal walking and posture, and behaviours similar to those of early Parkinson’s disease (PD), reduced number of nigrostriatal DA neurons and proapoptotic shifts in the survival/death proteins in midbrain and striatum. Contrary to young pk−/− animals 24-month-old pk−/− mice do not have compensatory elevation of GSH in striatum, glutathione reductase (GR) and glutathione peroxidase (GPx) activities are increased and catalase unchanged. Aged pk−/− mice accumulate high levels of tau and fail to up-regulate CHIP and HSP70. Our results suggest that aged pk−/− mice lack of the compensatory mechanisms that maintain a relatively normal DA function in early adulthood. This study could help to explain the effects of ageing in patients with genetic risks for Parkinson’s disease. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
42. More than just synaptic building blocks: scaffolding proteins of the post-synaptic density regulate dendritic patterning.
- Author
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Vessey, John P. and Karra, Daniela
- Subjects
PROTEINS ,ORGANIC compounds ,COMPARATIVE anatomy ,CELL morphology ,PATTERN formation (Physical sciences) ,NEUROTRANSMITTER receptors ,CYTOKINESIS ,NEURONS ,ACTIN - Abstract
The dendritic arbor is responsible for receiving and consolidating neuronal input. Outgrowth and morphogenesis of the arbor are complex stages of development that are poorly understood. However, recent findings have identified synaptic scaffolding proteins as novel regulators of these important events. Scaffolding proteins are enriched in the post-synaptic density where they bind and bring into close proximity neurotransmitter receptors, signaling molecules, and regulators of the actin cytoskeleton. This property is important for dendritic spine morphogenesis and maintenance in the mature neuron. Scaffolding proteins are now being described as key regulators of neurite outgrowth, dendritic development, and pattern formation in immature neurons. These proteins, which include post-synaptic-95, Shank and Densin-180, as well as many of their interacting partners, appear to regulate both the microtubule and actin cytoskeleton to influence dendrite morphology. Through a large array of protein–protein interaction domains, scaffolding proteins are able to form large macromolecular complexes that include cytoskeletal motor proteins as well as microtubule and actin regulatory molecules. Together, the new findings form a persuasive argument that scaffolding proteins deliver critical regulatory elements to sites of dendritic outgrowth and branching to modulate the formation and maintenance of the dendritic arbor. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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- View/download PDF
43. Selective re-routing of prion protein to proteasomes and alteration of its vesicular secretion prevent PrPSc formation.
- Author
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Filesi, Ilaria, Cardinale, Alessio, Mattei, Sonia, and Biocca, Silvia
- Subjects
PRIONS ,PROTEINS ,CELLS ,PRION diseases ,INTRACELLULAR pathogens ,SECRETION ,SCRAPIE - Abstract
Conversion of the cellular prion protein (PrP
C ) into the abnormal scrapie isoform (PrPSc ) is the hallmark of prion diseases, which are fatal and transmissible neurodegenerative disorders. ER-retained anti-prion recombinant single-chain Fv fragments have been proved to be an effective tool for inhibition of PrPC trafficking to the cell surface and antagonize PrPSc formation and infectivity. In the present study, we have generated the secreted version of 8H4 intrabody (Sec-8H4) in order to compel PrPC outside the cells. The stable expression of the Sec-8H4 intrabodies induces proteasome degradation of endogenous prion protein but does not influence its glycosylation profile and maturation. Moreover, we found a dramatic diverting of PrPC traffic from its vesicular secretion and, most importantly, a total inhibition of PrPSc accumulation in NGF-differentiated Sec-8H4 PC12 cells. These results confirm that perturbing the intracellular traffic of endogenous PrPC is an effective strategy to inhibit PrPSc accumulation and provide convincing evidences for application of intracellular antibodies in prion diseases. [ABSTRACT FROM AUTHOR]- Published
- 2007
- Full Text
- View/download PDF
44. Astrocytes aged in vitro show a decreased neuroprotective capacity.
- Author
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Pertusa, M., García-Matas, S., Rodríguez-Farré, E., Sanfeliu, C., and Cristòfol, R.
- Subjects
ASTROCYTES ,NERVOUS system ,NEUROSCIENCES ,NEUROCHEMISTRY ,PROTEINS - Abstract
Alterations in astrocyte function that may affect neuronal viability occur with brain aging. In this study, we evaluate the neuroprotective capacity of astrocytes in an experimental model of in vitro aging. Changes in oxidative stress, glutamate uptake and protein expression were evaluated in rat cortical astrocytes cultured for 10 and 90 days in vitro (DIV). Levels of glial fibrillary acidic protein and S100β increased at 90 days when cells were positive for the senescence β-galactosidase marker. In long-term astrocyte cultures, the generation of reactive oxygen species was enhanced and mitochondrial activity decreased. Simultaneously, there was an increase in proteins that stained positively for nitrotyrosine. The expression of Cu/Zn-superoxide dismutase (SOD-1) and haeme oxygenase-1 (HO-1) proteins and inducible nitric oxide synthase (iNOS) increased in aged astrocytes. Glutamate uptake in 90-DIV astrocytes was higher than in 10 DIV ones, and was more vulnerable to inhibition by H
2 O2 exposure. Enhanced glutamate uptake was probably because of up-regulation of the glutamate/aspartate transporter protein. Aged astrocytes had a reduced ability to maintain neuronal survival. These findings indicate that astrocytes may partially loose their neuroprotective ability during aging. The results also suggest that aged astrocytes may contribute to exacerbating neuronal injury in age-related neurodegenerative processes. [ABSTRACT FROM AUTHOR]- Published
- 2007
- Full Text
- View/download PDF
45. Localization of synaptic proteins involved in neurosecretion in different membrane microdomains.
- Author
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Taverna, Elena, Saba, Elena, Linetti, Anna, Longhi, Renato, Jeromin, Andreas, Righi, Marco, Clementi, Francesco, and Rosa, Patrizia
- Subjects
NEUROSECRETION ,PROTEINS ,EXOCYTOSIS ,CALCIUM channels ,G proteins ,NEUROENDOCRINE cells ,BRADYKININ - Abstract
A number of proteins and signalling molecules modulate voltage-gated calcium channel activity and neurosecretion. As recent findings have indicated the presence of Ca
v 2.1 (P/Q-type) channels and soluble N-ethyl-maleimide-sensitive fusion protein attachment protein receptors (SNAREs) in the cholesterol-enriched microdomains of neuroendocrine and neuronal cells, we investigated whether molecules known to modulate neurosecretion, such as the heterotrimeric G proteins and neuronal calcium sensor-1 (NCS-1), are also localized in these microdomains. After immuno-isolation, flotation gradients from Triton X-100-treated synaptosomal membranes revealed the presence of different detergent-resistant membranes (DRMs) containing proteins of the exocytic machinery (Cav 2.1 channels and SNAREs) or NCS-1; both DRM subtypes contained aliquots of heterotrimeric G protein subunits and phosphatidylinositol-4,5-bisphosphate. In line with the biochemical data, confocal imaging of immunolabelled membrane sheets revealed the localization of SNARE proteins and NCS-1 in different dot-like structures. This distribution was largely impaired by treatment with methyl-β-cyclodextrin, thus suggesting the localization of all three proteins in cholesterol-dependent domains. Finally, bradykinin (which is known to activate the NCS-1 pathway) caused a significant increase in NCS-1 in the DRMs. These findings suggest that different membrane microdomains are involved in the spatial organization of the complex molecular network that converges on calcium channels and the secretory machinery. [ABSTRACT FROM AUTHOR]- Published
- 2007
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- View/download PDF
46. Prion protein reduces both oxidative and non-oxidative copper toxicity.
- Author
-
Haigh, Cathryn L. and Brown, David R.
- Subjects
PRIONS ,PROTEINS ,GLYCOPROTEINS ,COPPER ,NEURODEGENERATION ,OXIDATIVE stress ,GLYCINE - Abstract
The prion protein is a membrane tethered glycoprotein that binds copper. Conversion to an abnormal isoform is associated with neurodegenerative diseases known as prion diseases. Expression of the prion protein has been suggested to prevent cell death caused by oxidative stress. Using cell based models we investigated the potential of the prion protein to protect against copper toxicity. Although prion protein expression effectively protected neurones from copper toxicity, this protection was not necessarily associated with reduction in oxidative damage. We also showed that glycine and the prion protein could both protect neuronal cells from oxidative stress. Only the prion protein could protect these cells from the toxicity of copper. In contrast glycine increased copper toxicity without any apparent oxidative stress or lipid peroxidation. Mutational analysis showed that protection by the prion protein was dependent upon the copper binding octameric repeat region. Our findings demonstrate that copper toxicity can be independent of measured oxidative stress and that prion protein expression primarily protects against copper toxicity independently of the mechanism of cell death. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
47. The LGI1/Epitempin gene encodes two protein isoforms differentially expressed in human brain.
- Author
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Furlan, Sandra, Roncaroli, Federico, Forner, Francesca, Vitiello, Libero, Calabria, Elisa, Piquer-Sirerol, Salomé, Valle, Giorgio, Perez-Tur, Jordi, Michelucci, Roberto, and Nobile, Carlo
- Subjects
LEUCINE ,GENES ,TEMPORAL lobe epilepsy ,PROTEINS ,HIPPOCAMPUS (Brain) - Abstract
The leucine-rich, glioma inactivated 1 (LGI1)/Epitempin gene has been linked to two phenotypes as different as gliomagenesis and autosomal dominant lateral temporal epilepsy. Its function and the biochemical features of the encoded protein are unknown. We characterized the LGI1/Epitempin protein product by western blot analysis of mouse and human brain tissues. Two proteins of about 60 and 65 kDa were detected by an anti-LGI1 antibody within the expected molecular mass range. The two proteins appeared to reside in different subcellular compartments, as they were fractionated by differential centrifugation. The specificity of both polypeptides was validated by cell transfection assay and mass spectrometry analysis. Immunoblot analysis of protein distribution in various zones of the human brain revealed variable amounts of both proteins. Notably, these proteins were more abundant in the temporal neocortex than in the hippocampus, the difference in abundance of the 65-kDa product being particularly pronounced. These results suggest that the two protein isoforms encoded by LGI1/Epitempin are differentially expressed in the human brain, and that higher expression levels of these proteins in the lateral temporal cortex may underlie the susceptibility of this brain region to the epileptogenic effects of LGI1/Epitempin mutations. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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- View/download PDF
48. The protein tyrosine phosphatase, Shp2, is required for the complete activation of the RAS/MAPK pathway by brain-derived neurotrophic factor.
- Author
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Easton, John B., Royer, Amanda R., and Middlemas, David S.
- Subjects
PROTEINS ,TYROSINE ,AMINO acids ,PHOSPHATASES ,NEUROTROPHINS ,BRAIN - Abstract
Brain-derived neurotrophic factor (BDNF) and other neurotrophins induce a unique prolonged activation of mitogen-activated protein kinase (MAPK) compared with growth factors. Characterization and kinetic and spatial modeling of the signaling pathways underlying this prolonged MAPK activation by BDNF will be important in understanding the physiological role of BDNF in many complex systems in the nervous system. In addition to Shc, fibroblast growth factor receptor substrate 2 (FRS2) is required for the BDNF-induced activation of MAPK. BDNF induces phosphorylation of FRS2. However, BDNF does not induce phosphorylation of FRS2 in cells expressing a deletion mutant of TrkB (TrkBΔPTB) missing the juxtamembrane NPXY motif. This motif is the binding site for SHC . NPXY is the consensus sequence for phosphotyrosine binding (PTB) domains, and notably, FRS2 and SHC contain PTB domains. This NPXY motif, which contains tyrosine 484 of TrkB, is therefore the binding site for both FRS2 and SHC. Moreover, the proline containing region (VIENP) of the NPXY motif is also required for FRS2 and SHC phosphorylation, which indicates this region is an important component of FRS2 and SHC recognition by TrkB. Previously, we had found that the phosphorylation of FRS2 induces association of FRS2 and growth factor receptor binding protein 2 (Grb2). Now, we have intriguing data that indicates BDNF induces association of the SH2 domain containing protein tyrosine phosphatase, Shp2, with FRS2. Moreover, the PTB association motif of TrkB containing tyrosine 484 is required for the BDNF-induced association of Shp2 with FRS2 and the phosphorylation of Shp2. These results imply that FRS2 and Shp2 are in a BDNF signaling pathway. Shp2 is required for complete MAPK activation by BDNF, as expression of a dominant negative Shp2 in cells attenuates BDNF-induced activation of MAPK. Moreover, expression of a dominant negative Shp2 attenuates Ras activation showing that the protein tyrosine phosphatase is required for complete activation of MAPKs by BDNF. In conclusion, Shp2 regulates BDNF signaling through the MAPK pathway by regulating either Ras directly or alternatively, by signaling components upstream of Ras . Characterization of MAPK signaling controlled by BDNF is likely to be required to understand the complex physiological role of BDNF in neuronal systems ranging from the regulation of neuronal growth and survival to the regulation of synapses. [ABSTRACT FROM AUTHOR]
- Published
- 2006
- Full Text
- View/download PDF
49. Ion interaction at the pore of Lc-type Ca2+ channel is sufficient to mediate depolarization-induced exocytosis.
- Author
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Lerner, Immanuel, Trus, Michael, Cohen, Roy, Yizhar, Ofer, Nussinovitch, Itzhak, and Atlas, Daphne
- Subjects
EXOCYTOSIS ,PROTEINS ,CATECHOLAMINES ,CHROMAFFIN cells ,IONS ,CELL physiology - Abstract
The coupling of voltage-gated Ca
2+ channel (VGCC) to exocytotic proteins suggests a regulatory function for the channel in depolarization-evoked exocytosis. To explore this possibility we have examined catecholamine secretion in PC12 and chromaffin cells. We found that replacing Ca2+ with La3+ or other lanthanide ions supported exocytosis in divalent ion-free solution. Cd2+ , nifedipine, or verapamil inhibited depolarization-evoked secretion in La3+ , indicating specific binding of La3+ at the pore of L-type VGCC, probably at the poly-glutamate (EEEE) locus. Lanthanide efficacy was stringently dependent on ionic radius with La3+ > Ce3+ > Pr3+ , consistent with a size-selective binding interface of trivalent cations at the channel pore. La3+ inward currents were not detected and the highly sensitive La3+ /fura-2 imaging assay (∼1 pm) detected no La3+ entry, cytosolic La3+ build-up, or alterations in cytosolic Ca2 . These results provide strong evidence that occupancy of the pore of the channel by an impermeable cation leads to a conformational change that is transmitted to the exocytotic machinery upstream of intracellular cation build-up (intracellular Ca2+ concentration). Our model allows for a tight temporal and spatial coupling between the excitatory stimulation event and vesicle fusion. It challenges the conventional view that intracellular Ca2+ ion build-up via VGCC permeation is required to trigger secretion and establishes the VGCC as a plausible Ca2+ sensor protein in the process of neuroendocrine secretion. [ABSTRACT FROM AUTHOR]- Published
- 2006
- Full Text
- View/download PDF
50. Basal somatodendritic dopamine release requires snare proteins.
- Author
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Fortin, Gabriel D., Desrosiers, Catherine C., Yamaguchi, Nobuharu, and Trudeau, Louis-Éric
- Subjects
DOPAMINE ,PROTEINS ,DOPAMINERGIC neurons ,BOTULINUM toxin ,CELL culture ,EXOCYTOSIS - Abstract
Dopaminergic neurons have the capacity to release dopamine not only from their axon terminals, but also from their somatodendritic compartment. The actual mechanism of somatodendritic dopamine release has remained controversial. Here we established for the first time a rat primary neuron culture model to investigate this phenomenon and use it to study the mechanism under conditions of non-stimulated spontaneous firing (1–2 Hz). We found that we can selectively measure somatodendritic dopamine release by lowering extracellular calcium to 0.5 mm, thus confirming the previously established differential calcium sensitivity of somatodendritic and terminal release. Dopamine release measured under these conditions was dependent on firing activity and independent of reverse transport through the plasma membrane. We found that treatment with botulinum neurotoxins A and B strongly reduced somatodendritic dopamine release, thus demonstrating the requirement for SNARE proteins SNAP-25 and synaptobrevin. Our work is the first to provide such direct and unambiguous evidence for the involvement of an exocytotic mechanism in basal spontaneous somatodendritic dopamine release. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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