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Vascular endothelial growth factor prevents G93A-SOD1-induced motor neuron degeneration

dc.contributor.authorLunn, J. Simonen_US
dc.contributor.authorSakowski, Stacey A.en_US
dc.contributor.authorKim, Bhumsooen_US
dc.contributor.authorRosenberg, Andrew A.en_US
dc.contributor.authorFeldman, Eva L.en_US
dc.date.accessioned2009-11-06T16:47:40Z
dc.date.available2010-03-01T21:10:28Zen_US
dc.date.issued2009-11en_US
dc.identifier.citationLunn, J. Simon; Sakowski, Stacey A.; Kim, Bhumsoo; Rosenberg, Andrew A.; Feldman, Eva L. (2009). "Vascular endothelial growth factor prevents G93A-SOD1-induced motor neuron degeneration." Developmental Neurobiology 69(13): 871-884. <http://hdl.handle.net/2027.42/64297>en_US
dc.identifier.issn1932-8451en_US
dc.identifier.issn1932-846Xen_US
dc.identifier.urihttps://hdl.handle.net/2027.42/64297
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=19672955&dopt=citationen_US
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by selective loss of motor neurons (MNs). Twenty percent of familial ALS cases are associated with mutations in Cu 2+ /Zn 2+ superoxide dismutase (SOD1). To specifically understand the cellular mechanisms underlying mutant SOD1 toxicity, we have established an in vitro model of ALS using rat primary MN cultures transfected with an adenoviral vector encoding a mutant SOD1, G93A-SOD1. Transfected cells undergo axonal degeneration and alterations in biochemical responses characteristic of cell death such as activation of caspase-3. Vascular endothelial growth factor (VEGF) is an angiogenic and neuroprotective growth factor that can increase axonal outgrowth, block neuronal apoptosis, and promote neurogenesis. Decreased VEGF gene expression in mice results in a phenotype similar to that seen in patients with ALS, thus linking loss of VEGF to the pathogenesis of MN degeneration. Decreased neurotrophic signals prior to and during disease progression may increase MN susceptibility to mutant SOD1-induced toxicity. In this study, we demonstrate a decrease in VEGF and VEGFR2 levels in the spinal cord of G93A-SOD1 ALS mice. Furthermore, in isolated MN cultures, VEGF alleviates the effects of G93A-SOD1 toxicity and neuroprotection involves phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling. Overall, these studies validate the usefulness of VEGF as a potential therapeutic factor for the treatment of ALS and give valuable insight into the responsible signaling pathways and mechanisms involved. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009en_US
dc.format.extent418811 bytes
dc.format.extent3118 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherLife and Medical Sciencesen_US
dc.subject.otherNeuroscience, Neurology and Psychiatryen_US
dc.titleVascular endothelial growth factor prevents G93A-SOD1-induced motor neuron degenerationen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelNeurosciencesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Neurology, University of Michigan, Ann Arbor, Michigan 48109en_US
dc.contributor.affiliationumDepartment of Neurology, University of Michigan, Ann Arbor, Michigan 48109en_US
dc.contributor.affiliationumDepartment of Neurology, University of Michigan, Ann Arbor, Michigan 48109en_US
dc.contributor.affiliationumDepartment of Neurology, University of Michigan, Ann Arbor, Michigan 48109en_US
dc.contributor.affiliationumDepartment of Neurology, University of Michigan, Ann Arbor, Michigan 48109 ; Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109en_US
dc.identifier.pmid19672955en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/64297/1/20747_ftp.pdf
dc.identifier.doi10.1002/dneu.20747en_US
dc.identifier.sourceDevelopmental Neurobiologyen_US
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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