Innovating Works

MyeliNANO

Financiado
Myelinic nanochannels in neurodegenerative diseases
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, i... 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. ver más
31/07/2021
MPG
3M€
Duración del proyecto: 68 meses Fecha Inicio: 2015-11-09
Fecha Fin: 2021-07-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2021-07-31
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-ADG-2014: ERC Advanced Grant
Cerrada hace 10 años
Presupuesto El presupuesto total del proyecto asciende a 3M€
Líder del proyecto
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Perfil tecnológico TRL 4-5