Estudio del mecanismo mediador de la diferenciación oligodendroglial inducido por Galectina-3

Galectin 3 (Gal-3) is a ?-galactosidase-binding lectin which favors the differentiation of oligodendrocytes (OLG), the myelin-forming cells in the CNS, and myelination through mechanisms not fully elucidated yet. In this doctoral thesis project, we have optimized methods for obtaining and purifying...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autor principal: Thomas, Laura
Otros Autores: Pasquini, Laura Andrea
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2019
Materias:
Akt
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2818
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2818.dir/2818.PDF
Aporte de:
Descripción
Sumario:Galectin 3 (Gal-3) is a ?-galactosidase-binding lectin which favors the differentiation of oligodendrocytes (OLG), the myelin-forming cells in the CNS, and myelination through mechanisms not fully elucidated yet. In this doctoral thesis project, we have optimized methods for obtaining and purifying functional recombinant Gal-3 (rGal-3) and have proven that rGal-3-treated OLG exhibit a higher rate of differentiation, a greater proportion of mature than immature cells and accelerated cytoskeleton dynamics through characteristic changes in actin polymerization. Such changes resulted from the influence of rGal-3 on Akt/mTOR, Erk 1/2 and ?-catenin signaling pathways. In addition, our studies succeeded in identifying a time window for rGal-3 actions, with OPC and pre-OLG as its principal targets in the promotion of oligodendroglial differentiation. Moreover, our results unveiled a wide range of molecules to which rGal-3 binds to exert pro-differentiating effects. Finally, assays on myelin quality allowed us to establish that OLG differentiated in the presence of rGal-3 are capable of effectively ensheathing both synthetic fibers and axons.