Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und Molekulare Biowissenschaften
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Nave, Klaus-Armin, Prof. Dr.


Professor of Molecular Biology, Director at the Max Planck Institute for Experimental Medicine
- 1987 PhD, University of California, San Diego
- 1987-1991 Postdoc, The Salk Institute, la Jolla, California
- 1991 Junior Group Leader, ZMBH, University of Heidelberg
- 1998 Professor of Molecular Biology (C4), ZMBH, University of Heidelberg
- 2000 Director, Department of Neurogenetics, Max Planck Institute for Experimental Medicine Göttingen and Professor of Biology, University of Heidelberg

Major Research Interests
We are interested in the mechanisms of neuron-glia interactions in the higher nervous system, and in the genes that are required for normal glial cell function. Here, transgenic and mutant mice have become important to study developmental processes as well as genetic diseases. For example, oligodendrocytes are glial cells highly specialized for enwrapping CNS axons with multiple layers of membranes, known to provide electrical insulation for rapid impulse propagation. We found that oligodendrocytes are also essential for maintaining the long-term integrity of myelinated axons, independent of the myelin function itself. The mechanisms by which oligodendrocytes support long-term axonal survival are still under investigation. The importance of glial cells as the "first line of neuroprotection", however, is illustrated by several myelin-associated diseases in which axonal neurodegeneration contribute to progressive disability. These range in humans from peripheral neuropathies (CMT1) to spastic paraplegia (SPG2), and presumably multiple sclerosis (MS) and certain forms of psychiatric disorders. We are developing transgenic animal models for some of these diseases, in order to dissect the underlying disease mechanisms and, in the case of CMT1A, have used these models to design novel therapeutic strategies.

The glial "decision" to myelinate an axonal segment is partly controlled by the axon itself, but the signaling mechanism is not understood. We have found that axonal neuregulin-1 (NRG1) is the major determinant of myelination in the peripheral nervous system. We are now investigating NRG1 dysregulation also in CNS myelination, using quantifiable behavioural functions in mice. By combining genetics with enviromental risk factors for schizophrenia (in collaboration with H. Ehrenreich) we will explore the hypothesis that NRG1, a known human schizophrenia susceptibility gene, points to an important role of myelinating glia in some psychiatric disorders.

Future Projects and Goals

Mechanisms of neuron-glia signalling; function of myelin proteins and lipids; transcriptional profiling of single cells in vivo; novel mouse models of neuropsychiatric disorders.

Homepage Department/Research Group:
http://www.em.mpg.de/index.php?id=34&no_cache=1

Selected Recent Publications

  • Nave KA (2010) Myelination and glial support of axonal integrity. Nature (in press)

  • Goebbels S, Oltrogge JH, Kemper R, Heilmann I, Bormuth I, Wolfer S, Wichert SP, Möbius W, Liu X, Lappe-Siefke C, Rossner MJ, Groszer M, Suter U, Frahm J, Boretius S, Nave KA (2010) Elevated phosphatidylinositol 3,4,5-trisphosphate in glia triggers cell-autonomous membrane wrapping and myelination. J Neurosci 30: 8953-8964

  • Nave KA (2010) Myelination and the trophic support of long axons. Nat Rev Neurosci 11: 275-283

  • Saher G, Quintes S, Möbius M, Wehr MC, Krämer-Albers EM, Brügger B, Nave KA (2009) Cholesterol regulates the ER exit of the major adhesion protein P0 in peripheral myelination. J Neurosci 29, 6094-6104

  • Brinkmann BG, Agarwal A, Sereda MW, Garratt AN, Müller T, Wende H, Stassart RM, Nawaz S, Humml C, Velanac V, Radyuschkin K, Goebbels S, Fischer TM, Franklin RJ, Lai C, Ehrenreich H, Birchmeier C, Schwab MH, Nave, KA (2008) Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system. Neuron 59: 581-595

  • Kassmann CM, Lappe-Siefke C, Baes M, Brügger B, Mildner A, Werner HB, Natt O, Michaelis Th, Prinz M, Frahm J, Nave KA (2007) Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes. Nat Genetics 39: 969-976

  • Werner HB, Kuhlmann K, Shen S, Uecker M, Schardt A, Dimova K, Orfaniotou F, Dhaunchak A, Brinkmann BG, Moebius W, Guarente L, Casaccia-Bonnefil P, Jahn O, Nave KA (2007) Proteolipid protein is required for transport of sirtuin 2 into CNS myelin. J Neurosci 27: 7717-7730

  • Saher G, Brugger B, Lappe-Siefke C, Mobius W, Tozawa R, Wehr MC, Wieland F, Ishibashi S, Nave KA (2005) High cholesterol level is essential for myelin membrane growth. Nat Neurosci 8: 468-475

  • Michailov G, Sereda V, MW, Brinkmann B, Fischer TM, Haug B, Birchmeier C, Role L, Lai C, Schwab MH, Nave KA (2004) Axonal neuregulin-1 regulates myelin sheath thickness. Science 304: 700-703




  • GGNB Nave

    Adresse
    Prof. Dr. Klaus-Armin Nave
    Abtl. Neurogenetik
    Max-Planck-Institut
    für Experimentelle Medizin
    Hermann-Rein-Str. 3
    37075 Göttingen
    Tel.: +49-(0)551-3899 757
    Fax: +49-(0)551-3899 758
    e-mail: nave@em.mpg.de

    GGNB-Zugehörigkeit
    Molecular Biology (IMPRS)
    Neurosciences (IMPRS)
    Genes and Development
    Molecular Physiology of the Brain (C
    MPB)

    Systems Neuroscience