Description du projet
La myéline: un acteur clé de la neurodégénérescence?
Les neurones du cerveau et de la moelle épinière sont isolés par une gaine de myéline qui peut considérablement augmenter la vitesse des impulsions électriques. La myéline est produite par les oligodendrocytes qui semblent jouer un rôle central dans l’intégrité des neurones en apportant des métabolites essentiels à la production d’énergie neuronale. Cela suggère que les oligodendrocytes pourraient avoir un impact sur les troubles neurologiques impliquant une démyélinisation, tels que la sclérose en plaques. Financé par le Conseil européen de la recherche, le projet MyeliNANO se propose d’étudier le rôle de la myéline dans les fonctions cérébrales supérieures et la mesure dans laquelle les oligodendrocytes influencent l’intégrité fonctionnelle des neurones et la neurodégénérescence. Les résultats serviront de base à une potentielle stratégie thérapeutique de neuroprotection métabolique pour les maladies neurodégénératives.
Objectif
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.
Champ scientifique
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- medical and health scienceshealth sciencesinflammatory diseases
- medical and health sciencesbasic medicineimmunologyimmunisation
- medical and health sciencesbasic medicineneurologymultiple sclerosis
- medical and health sciencesbasic medicineneurologyamyotrophic lateral sclerosis
Programme(s)
Thème(s)
Régime de financement
ERC-ADG - Advanced GrantInstitution d’accueil
80539 Munchen
Allemagne