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  • Cell Line  (6)
  • Mutation  (6)
  • Computer Simulation  (5)
  • American Association for the Advancement of Science (AAAS)  (12)
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  • 11
    Publikationsdatum: 2009-02-14
    Beschreibung: Deposition of the amyloid-beta peptide is a pathological hallmark of Alzheimer's disease. A high-throughput functional genomics screen identified G protein-coupled receptor 3 (GPR3), a constitutively active orphan G protein-coupled receptor, as a modulator of amyloid-beta production. Overexpression of GPR3 stimulated amyloid-beta production, whereas genetic ablation of GPR3 prevented accumulation of the amyloid-beta peptide in vitro and in an Alzheimer's disease mouse model. GPR3 expression led to increased formation and cell-surface localization of the mature gamma-secretase complex in the absence of an effect on Notch processing. GPR3 is highly expressed in areas of the normal human brain implicated in Alzheimer's disease and is elevated in the sporadic Alzheimer's disease brain. Thus, GPR3 represents a potential therapeutic target for the treatment of Alzheimer's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thathiah, Amantha -- Spittaels, Kurt -- Hoffmann, Marcel -- Staes, Mik -- Cohen, Adrian -- Horre, Katrien -- Vanbrabant, Mieke -- Coun, Frea -- Baekelandt, Veerle -- Delacourte, Andre -- Fischer, David F -- Pollet, Dirk -- De Strooper, Bart -- Merchiers, Pascal -- New York, N.Y. -- Science. 2009 Feb 13;323(5916):946-51. doi: 10.1126/science.1160649.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Developmental Genetics, Vlaams Institute for Biotechnology, Center for Human Genetics, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19213921" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adult ; Aged ; Amyloid Precursor Protein Secretases/metabolism ; Amyloid beta-Peptides/*biosynthesis ; Animals ; Cell Line ; Cell Line, Tumor ; Cells, Cultured ; Female ; Humans ; Male ; Mice ; Middle Aged ; Neurons/*metabolism ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/*metabolism ; Receptors, Notch/metabolism ; Signal Transduction
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 12
    Publikationsdatum: 2014-12-17
    Beschreibung: Stochasticity inherent to biochemical reactions (intrinsic noise) and variability in cellular states (extrinsic noise) degrade information transmitted through signaling networks. We analyzed the ability of temporal signal modulation--that is, dynamics--to reduce noise-induced information loss. In the extracellular signal-regulated kinase (ERK), calcium (Ca(2+)), and nuclear factor kappa-B (NF-kappaB) pathways, response dynamics resulted in significantly greater information transmission capacities compared to nondynamic responses. Theoretical analysis demonstrated that signaling dynamics has a key role in overcoming extrinsic noise. Experimental measurements of information transmission in the ERK network under varying signal-to-noise levels confirmed our predictions and showed that signaling dynamics mitigate, and can potentially eliminate, extrinsic noise-induced information loss. By curbing the information-degrading effects of cell-to-cell variability, dynamic responses substantially increase the accuracy of biochemical signaling networks.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Selimkhanov, Jangir -- Taylor, Brooks -- Yao, Jason -- Pilko, Anna -- Albeck, John -- Hoffmann, Alexander -- Tsimring, Lev -- Wollman, Roy -- P50 GM085764/GM/NIGMS NIH HHS/ -- P50-GM085764/GM/NIGMS NIH HHS/ -- R01 GM089976/GM/NIGMS NIH HHS/ -- R01-GM071573/GM/NIGMS NIH HHS/ -- R01-GM089976/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1370-3. doi: 10.1126/science.1254933.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Bioengineering, University of California-San Diego, La Jolla, CA 92093, USA. ; Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA 92093, USA. ; Department of Molecular and Cellular Biology, University of California-Davis, Davis 95616, USA. ; San Diego Center for Systems Biology, La Jolla, CA 92093, USA. Institute for Quantitative and Computational Biosciences and Department of Microbiology, Immunology, and Molecular Genetics, University of California-Los Angeles, Los Angeles, CA 90025, USA. ; San Diego Center for Systems Biology, La Jolla, CA 92093, USA. BioCircuits Institute, University of California-San Diego, La Jolla, CA 92093, USA. ; Department of Chemistry and Biochemistry, University of California-San Diego, La Jolla, CA 92093, USA. San Diego Center for Systems Biology, La Jolla, CA 92093, USA. Cell and Developmental Biology Section, Division of Biological Sciences, University of California-San Diego, La Jolla, CA 92093, USA. rwollman@ucsd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504722" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): *Calcium Signaling ; Cell Line ; Computer Simulation ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Humans ; *MAP Kinase Signaling System ; NF-kappa B/*metabolism ; *Signal Transduction ; Signal-To-Noise Ratio ; Single-Cell Analysis ; Systems Biology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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