Descripción del proyecto
La mielina: ¿factor clave de la neurodegeneración?
Las neuronas del cerebro y la médula espinal están aisladas por una vaina de mielina que puede aumentar muchísimo la velocidad de los impulsos eléctricos. La mielina es producida por los oligodendrocitos, que parecen desempeñar un papel fundamental en la integridad de las neuronas al proporcionar los metabolitos esenciales necesarios para la producción de energía neuronal. Ello sugiere que los oligodendrocitos podrían estar implicados en los trastornos neurológicos desmielinizantes como, por ejemplo, la esclerosis múltiple. En el proyecto MyeliNANO, financiado por el Consejo Europeo de Investigación, se pretende investigar el papel de la mielina en las funciones cerebrales superiores, así como hasta qué punto los oligodendrocitos influyen en la integridad funcional de las neuronas y la neurodegeneración. Los resultados allanarán el camino hacia la neuroprotección metabólica como posible tratamiento de las enfermedades neurodegenerativas.
Objetivo
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.
Ámbito científico
- 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
Programa(s)
Régimen de financiación
ERC-ADG - Advanced GrantInstitución de acogida
80539 Munchen
Alemania