Serum matrix metalloproteinase-9 activity is dysregulated with disease progression in the mutant SOD1 transgenic mice

Cynthia P W Soon, Peter J. Crouch, Bradley J. Turner, Catriona A. McLean, Katrina M. Laughton, Julie D. Atkin, Colin L. Masters, Anthony R. White, Qiao Xin Li

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 TgSOD1G93A 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 TgSOD1G93A mice with end-stage disease. These results were confirmed in serum of a high copy number strain of TgSOD1G93A 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.

LanguageEnglish
Pages260-266
Number of pages7
JournalNeuromuscular Disorders
Volume20
Issue number4
DOIs
Publication statusPublished - Apr 2010
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 9
Transgenic Mice
Disease Progression
Serum
Amyotrophic Lateral Sclerosis
Biomarkers
Motor Neurons
Spinal Cord
Neuropil
Matrix Metalloproteinases
Transgenes
Neuroglia
Neurodegenerative Diseases
Cerebral Cortex
Brain Stem

Cite this

Soon, Cynthia P W ; Crouch, Peter J. ; Turner, Bradley J. ; McLean, Catriona A. ; Laughton, Katrina M. ; Atkin, Julie D. ; Masters, Colin L. ; White, Anthony R. ; Li, Qiao Xin. / Serum matrix metalloproteinase-9 activity is dysregulated with disease progression in the mutant SOD1 transgenic mice. In: Neuromuscular Disorders. 2010 ; Vol. 20, No. 4. pp. 260-266.
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abstract = "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 TgSOD1G93A 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 TgSOD1G93A mice with end-stage disease. These results were confirmed in serum of a high copy number strain of TgSOD1G93A 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.",
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Soon, CPW, Crouch, PJ, Turner, BJ, McLean, CA, Laughton, KM, Atkin, JD, Masters, CL, White, AR & Li, QX 2010, 'Serum matrix metalloproteinase-9 activity is dysregulated with disease progression in the mutant SOD1 transgenic mice', Neuromuscular Disorders, vol. 20, no. 4, pp. 260-266. https://doi.org/10.1016/j.nmd.2009.11.015

Serum matrix metalloproteinase-9 activity is dysregulated with disease progression in the mutant SOD1 transgenic mice. / Soon, Cynthia P W; Crouch, Peter J.; Turner, Bradley J.; McLean, Catriona A.; Laughton, Katrina M.; Atkin, Julie D.; Masters, Colin L.; White, Anthony R.; Li, Qiao Xin.

In: Neuromuscular Disorders, Vol. 20, No. 4, 04.2010, p. 260-266.

Research output: Contribution to journalArticleResearchpeer-review

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