Activation of Phosphotyrosine-Mediated Signaling Pathways in the Cortex and Spinal Cord of SOD1G93A , a Mouse Model of Familial Amyotrophic Lateral Sclerosis

Neural Plasticity
Cinzia MallozziMaria Rosaria Domenici

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

Jan 1, 1995·Annual Review of Physiology·J Garthwaite, C L Boulton
Oct 1, 1995·Journal of the Neurological Sciences·J R LeeS H Appel
Dec 31, 1997·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C MallozziM Minetti
Jan 14, 1998·Neuron·E B Ziff
Aug 19, 1999·FEBS Letters·C MallozziM Minetti
Nov 21, 2001·Nature Reviews. Neuroscience·D W Cleveland, J D Rothstein
Sep 5, 2002·Free Radical Biology & Medicine·Maurizio MinettiA M Michela Di Stasi
Jun 26, 2004·Annual Review of Neuroscience·Lucie I BruijnDon W Cleveland
Oct 17, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yang ZhangPaul J Lombroso
Oct 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yongfang ZhangPaul J Lombroso
Oct 7, 2011·Clinical and Experimental Pharmacology & Physiology·Mohammed I HossainHeung-Chin Cheng
Oct 13, 2011·Nature Reviews. Neurology·Orla HardimanMatthew C Kiernan
Mar 16, 2012·The Cochrane Database of Systematic Reviews·Robert G MillerDan H Moore
May 1, 2012·The Journal of Biological Chemistry·Jian XuPaul J Lombroso
Dec 4, 2012·Biochimica Et Biophysica Acta·Alida SpalloniPatrizia Longone
Aug 24, 2013·Neurobiology of Disease·Kim A StaatsLudo Van Den Bosch
Aug 28, 2014·Stroke; a Journal of Cerebral Circulation·Renatta KnoxXiangning Jiang
Feb 25, 2015·Annals of Neurology·Adam C KaufmanStephen M Strittmatter
Nov 20, 2015·Experimental Neurology·Anna E KingJames C Vickers
Jan 7, 2016·Frontiers in Neuroscience·Jan Lewerenz, Pamela Maher
Feb 9, 2016·Nature Neuroscience·Nicholas L WeilingerRoger J Thompson
May 18, 2016·Neural Plasticity·Marija KamcevaPaul J Lombroso

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Citations

Aug 2, 2020·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Hazem AhmedSimon M Ametamey

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Methods Mentioned

BETA
transgenic
dissection
X-ray
phosphatase assay

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