Myelin-associated glycoprotein activation triggers glutamate uptake by oligodendrocytes and mitigates excitotoxicity

VIVINETTO A.; GARCIA KELLER, C; PALANDRI A.; CRISTIAN FALCON; CASTAÑARES CLARA; MOYANO A. L.; ROZES SALVADOR V.; ROJAS J.; PATRUCCO L.; MONFERRAN C; CANCELA LILIANA M; CRISTIANO E; SCHNAAR R; LOPEZ P.

BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2019

0925-4439

ACKGROUND: Myelin-associated glycoprotein (MAG) is a keymolecule involved in the nurturing effect of myelin on ensheathed axons.MAG also inhibits axon outgrowth after injury. In preclinical strokemodels, administration of a function-blocking anti-MAG monoclonalantibody (mAb) aimed to improve axon regeneration demonstrated reducedlesion volumes and a rapid clinical improvement, suggesting a mechanismof immediate neuroprotection rather than enhanced axon regeneration. Inaddition, it has been reported that antibody-mediated crosslinking of MAGcan protect oligodendrocytes (OLs) against glutamate (Glu) overload byunknown mechanisms. PURPOSE: To unravel the molecular mechanismsunderlying the protective effect of anti-MAG therapy with a focus onneuroprotection against Glu toxicity. RESULTS: MAG activation (viaantibody crosslinking) triggered the clearance of extracellular Glu byits uptake into OLs via high affinity excitatory amino acid transporters.This resulted not only in protection of OL