Nonhematopoietic erythropoietin derivatives prevent motoneuron degeneration in vitro and in vivo

Tiziana Mennini, Massimiliano De Paola, Paolo Bigini, Cristina Mastrotto, Elena Fumagalli, Sara Barbera, Manuela Mengozzi, Barbara Viviani, Emanuela Corsini, Marina Marinovich, Lars Torup, Johan Van Beek, Marcel Leist, Michael Brines, Antony Cerami, Pietro Ghezzi

Research output: Contribution to journalArticle

Abstract

Chronic treatment with asialo erythropoietin (ASIALO-EPO) or carbamylated erythropoietin (CEPO) improved motor behavior and reduced motoneuron loss and astrocyte and microglia activation in the cervical spinal cord of wobbler mice, an animal model of amyotrophic lateral sclerosis, but had no effect on hematocrit values. ASIALO-EPO and CEPO, like the parent compound EPO, protected primary motoneuron cultures from kainate-induced death in vitro. Both EPO receptor and the common CD131 β chain were expressed in cultured motoneurons and in the anterior horn of wobbler mice spinal cord. Our results strongly support a role for the common β chain CD131 in the protective effect of EPO derivatives on motoneuron degeneration. Thus CEPO, which does not bind to the classical homodimeric EPO receptor and is devoid of hematopoietic activity, could be effective in chronic treatment aimed at reducing motoneuron degeneration.

Original languageEnglish
Pages (from-to)153-160
Number of pages8
JournalMolecular medicine (Cambridge, Mass.)
Volume12
Issue number7-8
DOIs
Publication statusPublished - Jul 2006

ASJC Scopus subject areas

  • Genetics

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    Mennini, T., De Paola, M., Bigini, P., Mastrotto, C., Fumagalli, E., Barbera, S., Mengozzi, M., Viviani, B., Corsini, E., Marinovich, M., Torup, L., Van Beek, J., Leist, M., Brines, M., Cerami, A., & Ghezzi, P. (2006). Nonhematopoietic erythropoietin derivatives prevent motoneuron degeneration in vitro and in vivo. Molecular medicine (Cambridge, Mass.), 12(7-8), 153-160. https://doi.org/10.2119/2006-00045.Mennini