title: Acute administration of ucf-101 ameliorates the locomotor impairments induced by a traumatic spinal cord injury.
abstract: Secondary death of neural cells plays a key role in the physiopathology and the functional consequences of traumatic spinal cord injury (SCI). Pharmacological manipulation of cell death pathways leading to the preservation of neural cells is acknowledged as a main therapeutic goal in SCI. In the present work, we hypothesize that administration of the neuroprotective cell-permeable compound ucf-101 will reduce neural cell death during the secondary damage of SCI, increasing tissue preservation and reducing the functional deficits. To test this hypothesis, we treated mice with ucf-101 during the first week after a moderate contusive SCI. Our results reveal that ucf-101 administration protects neural cells from the deleterious secondary mechanisms triggered by the trauma, reducing the extension of tissue damage and improving motor function recovery. Our studies also suggest that the effects of ucf-101 may be mediated through the inhibition of HtrA2/OMI and the concomitant increase of inhibitor of apoptosis protein XIAP, as well as the induction of ERK1/2 activation and/or expression. In vitro assays confirm the effects of ucf-101 on both pathways as well as on the reduction of caspase cascade activation and apoptotic cell death in a neuroblastoma cell line. These results suggest that ucf-101 can be a promising therapeutic tool for SCI that deserves more detailed analyses.
authors.affiliation: Molecular Neuroprotection Group, Experimental Neurology Unit, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda s/n, 45071 Toledo, Spain. Electronic address: dreigada@sescam.jccm.es.
authors.forename: D
authors.initials: D
authors.lastname: Reigada
authors.affiliation: Molecular Neuroprotection Group, Experimental Neurology Unit, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda s/n, 45071 Toledo, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Nieto-Díaz
authors.affiliation: Molecular Neuroprotection Group, Experimental Neurology Unit, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda s/n, 45071 Toledo, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Navarro-Ruiz
authors.affiliation: Molecular Neuroprotection Group, Experimental Neurology Unit, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda s/n, 45071 Toledo, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Caballero-López
authors.affiliation: Molecular Neuroprotection Group, Experimental Neurology Unit, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda s/n, 45071 Toledo, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Del Águila
authors.affiliation: Molecular Neuroprotection Group, Experimental Neurology Unit, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda s/n, 45071 Toledo, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Muñoz-Galdeano
authors.affiliation: Molecular Neuroprotection Group, Experimental Neurology Unit, Hospital Nacional de Parapléjicos (SESCAM), Finca La Peraleda s/n, 45071 Toledo, Spain. Electronic address: rodrigom@sescam.jccm.es.
authors.forename: R M
authors.initials: RM
authors.lastname: Maza
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013871:Thiones / Q000494:pharmacology*
chemical_list: C107521:Birc4 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D018696:Neuroprotective Agents; D011744:Pyrimidinones; D013871:Thiones; C501517:UCF 101; D020169:Caspases
keywords: HtrA2/OMI; XIAP; apoptosis; neuroprotection; pERK1/2; spinal cord