Abstract
Granzyme A (gzmA), a serine protease involved in the modulation of the inflammatory immune response, is found at an elevated level in the serum from ALS patients. However, the influence of gzmA on the progression of ALS remains unclear. The aim of our work was to assess whether the absence of gzmA in an ALS murine model could help slow down the progression of the disease. Homozygous and hemizygous gzmA-deficient mice expressing the hSOD1G93A transgene were generated, and survival of these mice was monitored. Subsequently, gene and protein expression of inflammatory and oxidative stress markers was measured in the spinal cord and quadriceps of these mice. We observed the longest lifespan in gzmA+/− mice. GzmA gene and protein expression was downregulated in the spinal cord and serum from gmzA+/− mice, confirming that the increased survival of hemizygous mice is correlated with lower levels of gzmA. In addition, mRNA and protein levels of glutathione reductase (GSR), involved in oxidative stress, were found downregulated in the spinal cord and quadriceps of gmzA+/− mice, together with lower IL-1β and IL-6 mRNA levels in hemyzigous mice. In summary, our findings indicate for the first time that reduced levels, but not the absence, of gzmA could slightly ameliorate the disease progression in this animal model.
Funder
Instituto de Salud Carlos III
Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa” from the European Union, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
Consolidated Groups from Gobierno de Aragón
Departamento de Industria e Innovación from Gobierno de Aragón and Fondo Social Europeo
FEDER
Gobierno de Aragon
Ministerio de Ciencia, Innovacion y Universidades
Agencia Estatal de Investigación
Postdoctoral Juan de la Cierva Contract
CIBER -Consorcio Centro de Investigación Biomédica en Red
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Cited by
2 articles.
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