Advertisement

  • R‐flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice
    1. Katja Schmitz1,
    2. Natasja de Bruin2,,
    3. Philipp Bishay1,,
    4. Julia Männich1,
    5. Annett Häussler1,
    6. Christine Altmann1,
    7. Nerea Ferreirós1,
    8. Jörn Lötsch1,2,
    9. Alfred Ultsch3,
    10. Michael J Parnham2,
    11. Gerd Geisslinger1,2 and
    12. Irmgard Tegeder*,1,2
    1. 1Institute of Clinical Pharmacology Goethe‐University Hospital, Frankfurt am Main, Germany
    2. 2Fraunhofer Institute of Molecular Biology and Applied Ecology Project Group Translational Medicine and Pharmacology (IME‐TMP), Frankfurt am Main, Germany
    3. 3DataBionics Research Group, University of Marburg, Marburg, Germany
    1. *Corresponding author. Tel: +49 69 6301 7621; Fax: +49 69 6301 7636; E‐mail: tegeder{at}em.uni-frankfurt.de
    1. These authors contributed equally to this work

    R‐flurbiprofen treatment of experimental autoimmune encephalomyelitis in mouse models of multiple sclerosis prevented and attenuated relapsing‐remitting and primary progressive EAE, suggesting that R‐flurbiprofen could restore motor functions and alleviate MS‐associated chronic pain in humans.

    Synopsis

    R‐flurbiprofen treatment of experimental autoimmune encephalomyelitis in mouse models of multiple sclerosis prevented and attenuated relapsing‐remitting and primary progressive EAE, suggesting that R‐flurbiprofen could restore motor functions and alleviate MS‐associated chronic pain in humans.

    • R‐flurbiprofen favored regulatory and inflammation‐resolving immune cells and reduced myelin and axon destruction

    • R‐flurbiprofen increased anti‐inflammatory endocannabinoids in the periphery and central nervous system and reduced pro‐inflammatory lipid signaling molecules

    • Effects are likely mediated through a multi‐targeted reduction of pro‐inflammatory gene transcription, anti‐oxidative neuroprotection and favoring of inflammation‐resolving lipid signaling molecules

    • endocannabinoids
    • multiple sclerosis
    • optic neuritis
    • pain
    • regulatory T cells
    • Received March 14, 2014.
    • Revision received August 28, 2014.
    • Accepted August 29, 2014.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Katja Schmitz, Natasja de Bruin, Philipp Bishay, Julia Männich, Annett Häussler, Christine Altmann, Nerea Ferreirós, Jörn Lötsch, Alfred Ultsch, Michael J Parnham, Gerd Geisslinger, Irmgard Tegeder
  • N‐WASP is required for Amphiphysin‐2/BIN1‐dependent nuclear positioning and triad organization in skeletal muscle and is involved in the pathophysiology of centronuclear myopathy
    1. Sestina Falcone*,1,28,
    2. William Roman18,
    3. Karim Hnia3,
    4. Vincent Gache1,2,
    5. Nathalie Didier18,
    6. Jeanne Lainé28,
    7. Frederic Auradé18,
    8. Isabelle Marty5,
    9. Ichizo Nishino6,
    10. Nicolas Charlet‐Berguerand3,
    11. Norma Beatriz Romero48,
    12. Giovanna Marazzi1,
    13. David Sassoon1,
    14. Jocelyn Laporte3 and
    15. Edgar R Gomes*,1,2,78
    1. 1Myology Group, UMR S 787 INSERM, Université Pierre et Marie Curie Paris 6, Paris, France
    2. 2Institut de Myologie, Groupe Hospitalier Pitié‐Salpêtrière, Paris, France
    3. 3IGBMC‐CNRS, UMR 7104 INSERM U964, Illkirch, France
    4. 4Morphology Unit, Myology Institut Pitié Salpêtrière Hospital, Paris, France
    5. 5INSERM U836, Grenoble Institut des Neurosciences, Equipe Muscle et Pathologies, Grenoble, France
    6. 6National Center of Neurology and Psychiatry, Tokyo, Japan
    7. 7Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal
    8. 8Sorbonne Universités UPMC ‐ INSERM UMRS 974, CNRS FRE 3617 Myology Research Center, Paris, France
    1. * Corresponding author. Tel: +33 1 40 77 96 31; E‐mail: sestinaf{at}gmail.com

      Corresponding author. Tel: +33 1 40 77 96 87; E‐mail: edgar.gomes{at}upmc.fr

    1. These authors contributed equally to this work

    Amphiphysin‐2/BIN1 is known to associate with centronuclear myopathy (CNM) and myotonic dystrophy. N‐WASP is found downstream of Amphiphysin‐2/BIN1 and aberrantly distributed in skeletal muscle of patients. Activation of N‐WASP could provide a therapeutic option for CNM.

    Synopsis

    Amphiphysin‐2/BIN1 is known to associate with centronuclear myopathy (CNM) and myotonic dystrophy. N‐WASP is found downstream of Amphiphysin‐2/BIN1 and aberrantly distributed in skeletal muscle of patients. Activation of N‐WASP could provide a therapeutic option for CNM.

    • Amphiphysin‐2/BIN1 interacts with N‐WASP in skeletal muscle.

    • Amphiphysin‐2/BIN1 and N‐WASP are required for peripheral nuclei positioning and triad formation.

    • Peripheral nuclear positioning requires microtubule/Map7/Kif5b‐dependent distribution of nuclei along the myofiber and is driven by actin and nesprins.

    • centronuclear myopathy
    • cytoskeleton
    • nuclear movement
    • triad formation
    • Received July 15, 2014.
    • Revision received August 19, 2014.
    • Accepted August 26, 2014.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Sestina Falcone, William Roman, Karim Hnia, Vincent Gache, Nathalie Didier, Jeanne Lainé, Frederic Auradé, Isabelle Marty, Ichizo Nishino, Nicolas Charlet‐Berguerand, Norma Beatriz Romero, Giovanna Marazzi, David Sassoon, Jocelyn Laporte, Edgar R Gomes
  • ZIPCO, a putative metal ion transporter, is crucial for Plasmodium liver‐stage development
    1. Tejram Sahu1,2,
    2. Bertrand Boisson1,3,
    3. Céline Lacroix1,4,
    4. Emmanuel Bischoff5,
    5. Quentin Richier1,
    6. Pauline Formaglio1,
    7. Sabine Thiberge1,
    8. Irina Dobrescu1,
    9. Robert Ménard1 and
    10. Patricia Baldacci*,1
    1. 1Institut Pasteur Unité de Biologie et Génétique du Paludisme, Paris Cedex 15, France
    2. 2Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, Rockville, MD, USA
    3. 3St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY, USA
    4. 4Institut de Biologie et Chimie des Protéines, Lyon Cedex 07, France
    5. 5Institut Pasteur Plateforme Puces à ADN Génopole, Paris Cedex 15, France
    1. *Corresponding author. Tel: +33 1 44 38 94 95; E‐mail: patricia.baldacci{at}pasteur.fr

    ZIPCO is a novel Plasmodium berghei ZIP family protein, which might be involved in the transport of iron and possibly zinc. Parasites lacking ZIPCO present a normal blood phase but display a major developmental block in the host liver, which can be rescued by iron and zinc supplementation.

    Synopsis

    ZIPCO is a novel Plasmodium berghei ZIP family protein, which might be involved in the transport of iron and possibly zinc. Parasites lacking ZIPCO present a normal blood phase but display a major developmental block in the host liver, which can be rescued by iron and zinc supplementation.

    • ZIPCO is a newly identified Plasmodium protein belonging to the ZRT, IRT‐like Protein (ZIP) family.

    • Plasmodium berghei parasites lacking ZIPCO have no defect during the blood phase of malaria but display a major developmental block in the host liver.

    • The growth defect is rescued by iron and zinc supplementation.

    • This is first time that a ZIP protein has been shown to be important for the Plasmodium life cycle.

    • iron
    • liver stage
    • Plasmodium
    • transporter
    • ZIP
    • Received January 16, 2014.
    • Revision received July 23, 2014.
    • Accepted July 24, 2014.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Tejram Sahu, Bertrand Boisson, Céline Lacroix, Emmanuel Bischoff, Quentin Richier, Pauline Formaglio, Sabine Thiberge, Irina Dobrescu, Robert Ménard, Patricia Baldacci
  • Tumor cell‐specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase
    1. Stefanie Peter1,
    2. Jennyfer Bultinck2,
    3. Kevin Myant3,
    4. Laura A Jaenicke1,
    5. Susanne Walz1,
    6. Judith Müller4,
    7. Michael Gmachl5,
    8. Matthias Treu5,
    9. Guido Boehmelt5,
    10. Carsten P Ade1,
    11. Werner Schmitz1,
    12. Armin Wiegering6,
    13. Christoph Otto6,
    14. Nikita Popov1,7,
    15. Owen Sansom3,
    16. Norbert Kraut5 and
    17. Martin Eilers*,1,7
    1. 1Theodor Boveri Institute, Biocenter, University of Würzburg, Würzburg, Germany
    2. 2Cytokine Receptor Lab, Department of Biochemistry, Ghent University, Ghent, Belgium
    3. 3CRUK Beatson Institute, Glasgow, UK
    4. 4Department of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
    5. 5Department Lead Discovery, Boehringer Ingelheim RCV GmbH & Co KG, Vienna, Austria
    6. 6Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital Würzburg, Würzburg, Germany
    7. 7Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany
    1. *Corresponding author. Tel: +49 931 318 4111; E‐mail: martin.eilers{at}biozentrum.uni-wuerzburg.de

    New highly specific inhibitors of HUWE1 have been identified that can inhibit MYC function in a tumour cell‐specific manner, by preventing the HUWE1‐mediated block of a repressive complex of MYC with MIZ1 on MYC‐activated target genes.

    Synopsis

    New highly specific inhibitors of HUWE1 have been identified that can inhibit MYC function in a tumour cell‐specific manner, by preventing the HUWE1‐mediated block of a repressive complex of MYC with MIZ1 on MYC‐activated target genes.

    • HUWE1 is essential for growth of colorectal tumors in vivo and is globally required for expression of MYC target genes.

    • Small‐molecule inhibitors of HUWE1 inhibit expression of MYC target genes in a tumor‐cell specific manner.

    • Inhibition of HUWE1 stabilizes MIZ1 and induces global accumulation of MIZ1 on MYC‐bound target genes.

    • Accumulation of MIZ1 is required for repression of ribosomal protein genes upon HUWE1 inhibition.

    • colorectal cancer
    • HUWE1
    • MIZ1
    • MYC
    • ubiquitination
    • Received February 1, 2014.
    • Revision received July 30, 2014.
    • Accepted August 26, 2014.

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

    Stefanie Peter, Jennyfer Bultinck, Kevin Myant, Laura A Jaenicke, Susanne Walz, Judith Müller, Michael Gmachl, Matthias Treu, Guido Boehmelt, Carsten P Ade, Werner Schmitz, Armin Wiegering, Christoph Otto, Nikita Popov, Owen Sansom, Norbert Kraut, Martin Eilers