| Autor: |
Kiaei M; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA. mak2026@med.cornell.edu , Kipiani K, Calingasan NY, Wille E, Chen J, Heissig B, Rafii S, Lorenzl S, Beal MF |
| Jazyk: |
angličtina |
| Zdroj: |
Experimental neurology [Exp Neurol] 2007 May; Vol. 205 (1), pp. 74-81. Date of Electronic Publication: 2007 Feb 12. |
| DOI: |
10.1016/j.expneurol.2007.01.036 |
| Abstrakt: |
Whether increased levels of matrix metalloproteinases (MMPs) correspond to a role in the pathogenesis of amyotrophic lateral sclerosis (ALS) needs to be determined and it is actively being pursued. Here we present evidence suggesting that MMP-9 contributes to the motor neuron cell death in ALS. We examined the role of MMP-9 in a mouse model of familial ALS and found that lack of MMP-9 increased survival (31%) in G93A SOD1 mice. Also, MMP-9 deficiency in G93A mice significantly attenuated neuronal loss, and reduced neuronal TNF-alpha and FasL immunoreactivities in the lumbar spinal cord. These findings suggest that MMP-9 is an important player in the pathogenesis of ALS. Our data suggest that the mechanism for MMP-9 neurotoxicity in ALS may be by upregulating neuronal TNF-alpha and FasL expression and activation. This study provides new mechanism and suggests that MMP inhibitors may offer a new therapeutic strategy for ALS. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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