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.
| Language | English |
|---|---|
| Pages | 260-266 |
| Number of pages | 7 |
| Journal | Neuromuscular Disorders |
| Volume | 20 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2010 |
| Externally published | Yes |
Fingerprint
Cite this
}
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 journal › Article › Research › peer-review
TY - JOUR
T1 - Serum matrix metalloproteinase-9 activity is dysregulated with disease progression in the mutant SOD1 transgenic mice
AU - Soon, Cynthia P W
AU - Crouch, Peter J.
AU - Turner, Bradley J.
AU - McLean, Catriona A.
AU - Laughton, Katrina M.
AU - Atkin, Julie D.
AU - Masters, Colin L.
AU - White, Anthony R.
AU - Li, Qiao Xin
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77950955450&partnerID=8YFLogxK
U2 - 10.1016/j.nmd.2009.11.015
DO - 10.1016/j.nmd.2009.11.015
M3 - Article
VL - 20
SP - 260
EP - 266
JO - Neuromuscular Disorders
T2 - Neuromuscular Disorders
JF - Neuromuscular Disorders
SN - 0960-8966
IS - 4
ER -