title: Nonhematopoietic erythropoietin derivatives prevent motoneuron degeneration in vitro and in vivo.
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 beta 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 beta 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.
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute for Pharmacological Research, Milan, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mennini
authors.forename: Massimiliano
authors.initials: M
authors.lastname: De Paola
authors.forename: Paolo
authors.initials: P
authors.lastname: Bigini
authors.forename: Cristina
authors.initials: C
authors.lastname: Mastrotto
authors.forename: Elena
authors.initials: E
authors.lastname: Fumagalli
authors.forename: Sara
authors.initials: S
authors.lastname: Barbera
authors.forename: Manuela
authors.initials: M
authors.lastname: Mengozzi
authors.forename: Barbara
authors.initials: B
authors.lastname: Viviani
authors.forename: Emanuela
authors.initials: E
authors.lastname: Corsini
authors.forename: Marina
authors.initials: M
authors.lastname: Marinovich
authors.forename: Lars
authors.initials: L
authors.lastname: Torup
authors.forename: Johan
authors.initials: J
authors.lastname: Van Beek
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
authors.forename: Michael
authors.initials: M
authors.lastname: Brines
authors.forename: Antony
authors.initials: A
authors.lastname: Cerami
authors.forename: Pietro
authors.initials: P
authors.lastname: Ghezzi
mesh_terms: D000818:Animals; D001212:Asialoglycoproteins / Q000494:pharmacology*; D001522:Behavior, Animal; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053648:Cytokine Receptor Common beta Subunit / Q000378:metabolism; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006410:Hematopoiesis; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D008818:Mice, Neurologic Mutants; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D009410:Nerve Degeneration / Q000517:prevention & control*; D009414:Nerve Growth Factors / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000473:pathology
chemical_list: D001212:Asialoglycoproteins; D053648:Cytokine Receptor Common beta Subunit; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; C500605:asialoerythropoietin; C488171:carbamylated erythropoietin; D004921:Erythropoietin; D007608:Kainic Acid