MAG AS A THERAPEUTIC TARGET FOR NEURODEGENERATIVE DISEASES RELATED TO GLUTAMATE OVERLOAD

CASTAÑARES CN; VIVINETTO AL; LOPEZ PHH

Cordoba

Congreso; XXXIII Reunión Anual de la SAN; 2018

UNC

This research project analyzes the protective effect of oligodendrocytes (OLs) against excitotoxicity, focusing on their critical role as white matter extracellular glutamate modulators. Our group has previously demonstrated that crosslinking of MAG through monoclonal antibody clone 513 induce an intracellular signaling which results in protection of OLs and nearby neurons. Based in these previous findings, our aims are: to study the role of the Ca2+ -dependent intracellular signaling pathway and to probe new intracellular signaling pathways when MAG is pharmacologically activated. In addition, we seek to develop new bioactive ligands of MAG for therapeutic purposes and to evaluate the efficacy of anti-MAG therapy in animal models with axonal damage secondary to Glu-mediated toxicity and to demonstrate its efficacy in modulating Glu levels in the CNS. We propose multiple approaches in order to characterize such pathways and to assess therapeutic effects: OL-enriched primary culture, cerebellar organotypic culture, myelinating neuronal-OL co-culture, mass gene expression analysis techniques and EAE and stroke animal models. These studies can help to describe more precisely intracellular signaling pathways involved in axon-myelin interaction that provides stability and viability for both neurons and OL. Moreover they can contribute to the development of novel neuroprotective therapies in order to mitigate demyelination consequences such as axonal damage present in MS.