MyeliNANO SIGNED
Myelinic nanochannels in neurodegenerative diseases
Total Cost €
0EC-Contrib. €
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Project "MyeliNANO" data sheet
The following table provides information about the project.
| Coordinator |
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Organization address contact info |
| 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.
| # | ||||
|---|---|---|---|---|
| 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 |
|---|---|---|---|
| 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, MarÃa 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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