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MyeliNANO SIGNED

Myelinic nanochannels in neurodegenerative diseases

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EC-Contrib. €

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Partnership

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 MyeliNANO project word cloud

Explore the words cloud of the MyeliNANO project. It provides you a very rough idea of what is the project "MyeliNANO" about.

specialized    metabolically    myelinic    axons    neuropsychiatric    energy    axonassociated    nanochannels    mice    neuroinflammation    brain    tools    neurodegenerative    cellular    genetic    made    reducing    mitochondria    misfolded    absence    nanometer    intriguing    channels    300    hypothesize    metabolic    survival    paradigm    mechanisms    itself    oligodendrocytes    differen    sheath    space    functions    soma    fast    oligodendroglial    lost    therapeutic    disorders    neurological    metabolism    discovered    oligodendrocyte    axonal    mechanism    found    cytosolic    injury    risk    generate    perturbations    cns    atp    propagation    proteins    hypothesis    shift    aggregation    unknown    glia    underlying    shed    involve    transported    vulnerable    pave    physiological    pyruvate    opens    cells    glycolytic    metabolites    secondary    myelinated    diverse    previously    couple    lactate    neuroprotection    sclerosis    myelination    possibility    integrity    ultrastructure    impulse    function    compartment    diseases    physical    myelinano    adaxonal    glial    aging    independent    myelin    multiple    light    modifiers    combined   

Project "MyeliNANO" data sheet

The following table provides information about the project.

Coordinator
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV 

Organization address
address: HOFGARTENSTRASSE 8
city: Munich
postcode: 80539
website: www.mpg.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website http://www.em.mpg.de/index.php
 Total cost 2˙500˙000 €
 EC max contribution 2˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-04-01   to  2021-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (Munich) coordinator 2˙500˙000.00

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 Project objective

Myelin is made by highly specialized glial cells and enables fast axonal impulse propagation. We have discovered that oligodendrocytes in the CNS are, in addition to myelination, required for the integrity and survival of axons, independent of the presence or absence of myelin itself. More recently, we found the underlying mechanism and could show that glycolytic oligodendrocytes provide axons with pyruvate/lactate. These metabolites are transported through a system of myelinic nanochannels to the axonal compartment, in which mitochondria generate ATP. The finding was a paradigm-shift for the physiological function of axonassociated glia, and opens now the intriguing possibility that oligodendrocytes are important modifiers of neurological diseases in which myelinated axons are lost. This includes, in addition to multiple sclerosis, also classical neuropsychiatric disorders. We will generate novel genetic tools in mice that allow us to study the role myelin and secondary axonal loss in higher brain functions. We will test the challenging hypothesis that reducing oligodendroglial support of axonal metabolism is a risk for differen neurodegenerative disorders. These involve the previously neglected ultrastructure of CNS myelin with cytosolic (20-300 nanometer wide) channels within the myelin sheath. These 'nanochannels' couple the oligodendrocyte soma metabolically to the adaxonal space, but are vulnerable to aging and physical injury. We hypothesize that cellular mechanisms as diverse as neuroinflammation and the aggregation of misfolded proteins in myelinic nanochannels cause perturbations of the axonal energy metabolism. When combined, the findings of MyeliNANO will shed new light on previously unknown functions of CNS myelin and will pave the way for metabolic neuroprotection as a therapeutic approach to a range of neurodegenerative diseases.

 Publications

year authors and title journal last update
List of publications.
2019 Michelle S Erwig, Julia Patzig, Anna M Steyer, Payam Dibaj, Mareike Heilmann, Ingo Heilmann, Ramona B Jung, Kathrin Kusch, Wiebke Möbius, Olaf Jahn, Klaus-Armin Nave, Hauke B Werner
Anillin facilitates septin assembly to prevent pathological outfoldings of central nervous system myelin
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.43888
eLife 8 2019-06-06
2019 Robert Fledrich, Dagmar Akkermann, Vlad Schütza, Tamer A. Abdelaal, Doris Hermes, Erik Schäffner, M. Clara Soto-Bernardini, Tilmann Götze, Axel Klink, Kathrin Kusch, Martin Krueger, Theresa Kungl, Clara Frydrychowicz, Wiebke Möbius, Wolfgang Brück, Wolf C. Mueller, Ingo Bechmann, Michael W. Sereda, Markus H. Schwab, Klaus-Armin Nave, Ruth M. Stassart
NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-09385-6
Nature Communications 10/1 2019-06-06
2019 Sina K. Stumpf, Stefan A. Berghoff, Andrea Trevisiol, Lena Spieth, Tim Düking, Lennart V. Schneider, Lennart Schlaphoff, Steffi Dreha-Kulaczewski, Annette Bley, Dinah Burfeind, Kathrin Kusch, Miso Mitkovski, Torben Ruhwedel, Philipp Guder, Heiko Röhse, Jonas Denecke, Jutta Gärtner, Wiebke Möbius, Klaus-Armin Nave, Gesine Saher
Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus–Merzbacher disease
published pages: , ISSN: 0001-6322, DOI: 10.1007/s00401-019-01985-2
Acta Neuropathologica 2019-06-06
2018 R. Fledrich, T. Abdelaal, L. Rasch, V. Bansal, V. Schütza, B. Brügger, C. Lüchtenborg, T. Prukop, J. Stenzel, R. U. Rahman, D. Hermes, D. Ewers, W. Möbius, T. Ruhwedel, I. Katona, J. Weis, D. Klein, R. Martini, W. Brück, W. C. Müller, S. Bonn, I. Bechmann, K. A. Nave, R. M. Stassart, M. W. Sereda
Targeting myelin lipid metabolism as a potential therapeutic strategy in a model of CMT1A neuropathy
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-05420-0
Nature Communications 9/1 2019-04-18
2018 Hana Janova, Sahab Arinrad, Evan Balmuth, Marina Mitjans, Johannes Hertel, Mohamad Habes, Robert A. Bittner, Hong Pan, Sandra Goebbels, Martin Begemann, Ulrike C. Gerwig, Sönke Langner, Hauke B. Werner, Sarah Kittel-Schneider, Georg Homuth, Christos Davatzikos, Henry Völzke, Brian L. West, Andreas Reif, Hans Jörgen Grabe, Susann Boretius, Hannelore Ehrenreich, Klaus-Armin Nave
Microglia ablation alleviates myelin-associated catatonic signs in mice
published pages: 734-745, ISSN: 0021-9738, DOI: 10.1172/JCI97032
Journal of Clinical Investigation 128/2 2019-04-18
2018 Ruth M. Stassart, Wiebke Möbius, Klaus-Armin Nave, Julia M. Edgar
The Axon-Myelin Unit in Development and Degenerative Disease
published pages: , ISSN: 1662-453X, DOI: 10.3389/fnins.2018.00467
Frontiers in Neuroscience 12 2019-04-18
2018 Lucas Schirmer, Wiebke Möbius, Chao Zhao, Andrés Cruz-Herranz, Lucile Ben Haim, Christian Cordano, Lawrence R Shiow, Kevin W Kelley, Boguslawa Sadowski, Garrett Timmons, Anne-Katrin Pröbstel, Jackie N Wright, Jung Hyung Sin, Michael Devereux, Daniel E Morrison, Sandra M Chang, Khalida Sabeur, Ari J Green, Klaus-Armin Nave, Robin JM Franklin, David H Rowitch
Oligodendrocyte-encoded Kir4.1 function is required for axonal integrity
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.36428
eLife 7 2019-04-18
2018 Marie-Theres Weil, Saskia Heibeck, Mareike Töpperwien, Susanne tom Dieck, Torben Ruhwedel, Tim Salditt, María C. Rodicio, Jennifer R. Morgan, Klaus-Armin Nave, Wiebke Möbius, Hauke B. Werner
Axonal Ensheathment in the Nervous System of Lamprey: Implications for the Evolution of Myelinating Glia
published pages: 6586-6596, ISSN: 0270-6474, DOI: 10.1523/JNEUROSCI.1034-18.2018
The Journal of Neuroscience 38/29 2019-04-18
2017 Eva L. Feldman, Klaus-Armin Nave, Troels S. Jensen, David L.H. Bennett
New Horizons in Diabetic Neuropathy: Mechanisms, Bioenergetics, and Pain
published pages: 1296-1313, ISSN: 0896-6273, DOI: 10.1016/j.neuron.2017.02.005
Neuron 93/6 2019-04-18

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