Journal
NEUROMUSCULAR DISORDERS
Volume 20, Issue 4, Pages 260-266Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.nmd.2009.11.015
Keywords
Amyotrophic lateral sclerosis (ALS); Matrix metalloproteinase-9 (MMP-9); Matrix metalloproteinase-2 (MMP-2); Superoxide dismutase 1 (SOD1); Serum; Zymography; SOD1G93A transgenic mice
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Funding
- NHMRC [400202]
- CJ Martin Fellowship [359269]
- Bethlehem Griffiths Research Foundation
- Motor Neurone Disease Research Institute of Australia
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Amyotrophic lateral sclerosis (ALS) is an adult-onset fatal neurodegenerative disorder characterized by progressive deterioration of motor neurons in the spinal cord, brainstem, and cerebral cortex. Matrix metalloproteinase-9 (MMP-9) is proposed to be a biomarker for ALS due to a potential pathological role in the disease. However, despite numerous studies, it is still unclear whether there is a direct correlation between MMP-9 expression in serum and progression of disease. Therefore, we used a TgSOD1(G93A) mouse with a low transgene copy number. This model shows slow disease progression analogous to human ALS and provides a useful model to study biomarker expression at different stages of disease. Using zymography, we found that serum MMP-9 activity was significantly elevated in animals showing early signs of disease when compared to the younger, pre-symptomatic animals. This was followed by a decrease in MMP-9 activity in TgSOD1(G93A) mice with end-stage disease. These results were confirmed in serum of a high copy number strain of TgSOD1(G93A) mice with rapid progression. MMP-9 expression was changed accordingly in spinal motor neurons, glia and neuropil, suggesting a spinal cord contribution to blood MMP-9 activity. Serum MMP-2 activity followed a similar profile as the MMP-9 in these two models. These data indicate that circulating MMP-9 is altered throughout the course of disease progression in mice. Further studies in human ALS may validate the suitability of serum MMP-9 activity as a biomarker for early stage disease. (C) 2009 Elsevier B.V. All rights reserved.
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