title: Role of matrix metalloproteinase-9 in a mouse model for amyotrophic lateral sclerosis.
abstract: The pathogenesis of amyotrophic lateral sclerosis remains poorly understood, but microglial and astroglial activation are thought to contribute to motor neuron death. Evidence suggests that matrix metalloproteinase-9 (MMP-9) is a mediator of this deleterious effect. In this study, we evaluated the effect of MMP-9 on the pathogenesis of amyotrophic lateral sclerosis. Although marked microglial and astroglial proliferation was seen in the spinal cord and in-vitro studies proved MMP-9 to be produced by these cells, deletion of the MMP-9 gene in SOD1(G93A) mice accelerated rather than delayed the motor neuron disease and significantly reduced survival. Our results suggest that the effect of MMP-9 on mutant superoxide dismutase-1 (SOD1)-induced motor neuron disease is protective rather than hazardous. Therefore, the effect of pharmacological inhibition of MMP-9 activity is unlikely to be of therapeutical benefit in amyotrophic lateral sclerosis.
authors.affiliation: Laboratory for Neurobiology, Campus Gasthuisberg, Herestraat 49, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Maarten
authors.initials: M
authors.lastname: Dewil
authors.forename: Céline
authors.initials: C
authors.lastname: Schurmans
authors.forename: Sofie
authors.initials: S
authors.lastname: Starckx
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.forename: Ludo
authors.initials: L
authors.lastname: Van Den Bosch
authors.forename: Wim
authors.initials: W
authors.lastname: Robberecht
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000201:enzymology / Q000473:pathology; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D020780:Matrix Metalloproteinase 9