Astrocytes acquire resistance to iron-dependent oxidative stress upon proinflammatory activation

Romina Macco, Ilaria Pelizzoni, Alessandra Consonni, Ilaria Vitali, Giacomo Giacalone, Filippo Martinelli Boneschi, Franca Codazzi, Fabio Grohovaz, Daniele Zacchetti

Astrocytes respond to local insults within the brain and the spinal cord with important changes in their phenotype. This process, overall known as "activation", is observed upon proinflammatory stimulation and leads astrocytes to acquire either a detrimental phenotype, thereby contributing to the neurodegenerative process, or a protective phenotype, thus supporting neuronal survival. Within the mechanisms responsible for inflammatory neurodegeneration, oxidative stress plays a major role and has recently been recognized to be heavily influenced by changes in cytosolic iron levels. In this work, we investigated how activation affects the competence of astrocytes to handle iron overload and the ensuing oxidative stress.