Role of matrix metalloproteinase-9 in a mouse model for amyotrophic lateral sclerosis.
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.
Dewil
Maarten
M
Laboratory for Neurobiology, Campus Gasthuisberg, Herestraat 49, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Schurmans
Céline
C
Starckx
Sofie
S
Opdenakker
Ghislain
G
Van Den Bosch
Ludo
L
Robberecht
Wim
W
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
C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D020780:Matrix Metalloproteinase 9