Urinary-type plasminogen activator and its receptor is elevated in G93A Mice

Introduction: The plasminogen system is involved in proteolysis in brain injury and inflammation and may also contribute to the pathogenesis of neurodegenerative diseases as has recently been shown in Alzheimers disease and Creutzfeldt-Jacob disease. As yet, there has been little investigation of the role of the plasminogen activator system in amyotrophic lateral sclerosis (ALS).

Methods: We used zymography and PCR to analyze the expression of Urinary-type plasminogen activator (uPA) and its receptor (uPAR) in spinal cord tissue from G93A mice.

Results: PCR analysis of spinal cord of G93A mice showed, that expression of uPAR was increased during the progression of disease. Moreover uPA expression was increased in the spinal cord of G93A mice as compared to controls.

Treatment with an uPA-inhibitor did prolong survival time in G93A mice as compared to untreated animals (135 vs. 126 days).

Conclusions: Our experiments show, that uPAR and uPA are expressed in an animal model of ALS and treatment may extend survival time. Further studies are necessary to determine, whether treatment with an uPA inhibitor could provide a useful adjuvant therapeutic strategy in ALS.