Activation of Phosphotyrosine-Mediated Signaling Pathways in the Cortex and Spinal Cord of SOD1G93A , a Mouse Model of Familial Amyotrophic Lateral Sclerosis
Abstract
Degeneration of cortical and spinal motor neurons is the typical feature of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease for which a pathogenetic role for the Cu/Zn superoxide dismutase (SOD1) has been demonstrated. Mice overexpressing a mutated form of the SOD1 gene (SOD1G93A) develop a syndrome that closely resembles the human disease. The SOD1 mutations confer to this enzyme a "gain-of-function," leading to increased production of reactive oxygen species. Several oxidants induce tyrosine phosphorylation through direct stimulation of kinases and/or phosphatases. In this study, we analyzed the activities of src and fyn tyrosine kinases and of protein tyrosine phosphatases in synaptosomal fractions prepared from the motor cortex and spinal cord of transgenic mice expressing SOD1G93A. We found that (i) protein phosphotyrosine level is increased, (ii) src and fyn activities are upregulated, and (iii) the activity of tyrosine phosphatases, including the striatal-enriched tyrosine phosphatase (STEP), is significantly decreased. Moreover, the NMDA receptor (NMDAR) subunit GluN2B tyrosine phosphorylation was upregulated in SOD1G93A. Tyrosine phosphorylation of GluN2B subunits regulates the NMDAR functi...Continue Reading
References
Peroxynitrite activates kinases of the src family and upregulates tyrosine phosphorylation signaling
Citations
Methods Mentioned
Related Concepts
Related Feeds
ALS: Genetics
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.
ALS: Genetics
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.
Amyloid Lateral Sclerosis
Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.