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.
journal_name
Neuroreportjournal_title
Neuroreportauthors
Dewil M,Schurmans C,Starckx S,Opdenakker G,Van Den Bosch L,Robberecht Wdoi
10.1097/00001756-200503150-00003subject
Has Abstractpub_date
2005-03-15 00:00:00pages
321-4issue
4eissn
0959-4965issn
1473-558Xpii
00001756-200503150-00003journal_volume
16pub_type
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