Exp Neurol
Department of Neurology, University of Munich, Munich, Germany; Department of Neurology, University of Bonn, Bonn, Germany.
Published: October 2007
There is substantial evidence, implicating extracellular matrix (ECM) regulating enzymes in the pathogenesis of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). The most important ECM-degrading proteases are serine proteases (plasminogen activators, PA) and matrix metalloproteinases (MMPs). Since the role of MMPs in ALS has been addressed recently, we investigated the expression of the serine protease urokinase-type plasminogen activator (uPA) and its receptor in ALS. Employing rtPCR, zymography and immunohistochemistry we analyzed the expression of uPA and its receptor uPAR in spinal cord tissue of ALS cases and in the G93A SOD1 transgenic mouse. In the ventral horn of the spinal cord of ALS cases we found increased uPAR staining of motor neurons. In G93A mice, the expression profile of uPA and uPAR mRNA was significantly increased starting at the age of 90 days as compared to non-transgenic littermates. The uPA-dependent plasminogen activation in G93A mice at endstage increased markedly compared with controls and immunostaining of the spinal cord from G93A mice revealed increased uPAR immunostaining in neurons. To determine the functional role of uPA, we investigated the effect of intraperitoneal (i.p.) administration of the uPA inhibitor WX-340 (10 mg/kg), starting at the age of 30 days (n=18). Treatment with WX-340 prolonged (p<0.05) survival of the animals (135+/-2 vs. 126+/-3) as well as improving rotarod performance. Our experiments demonstrate that uPA and its receptor are expressed in ALS patients and in an animal model of ALS. Early inhibition with a synthetic uPA inhibitor prolonged the life of the transgenic animals. These findings indicate that the urokinase-type plasminogen activator system may play a role in the complex pathogenesis of ALS.
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http://dx.doi.org/10.1016/j.expneurol.2007.07.007 | DOI Listing |
Mol Biol Rep
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Department of Clinical Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
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January 2025
Department of Biomedical Engineering, College of Chemistry and Life Sciences, Beijing University of Technology, Beijing, 100124, China.
The brain undergoes atrophy and cognitive decline with advancing age. The utilization of brain age prediction represents a pioneering methodology in the examination of brain aging. This study aims to develop a deep learning model with high predictive accuracy and interpretability for brain age prediction tasks.
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January 2025
Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN, USA.
Background: Spinal cord (SC) atrophy is a key imaging biomarker of progressive multiple sclerosis (MS). Progressive MS is more common in men and postmenopausal women.
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January 2025
Rehabilitation Studies, Faculty of Medicine and Health, The University of Sydney, The Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia.
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Center for Neuroscience and Pain Research, Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
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