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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2003-8-18
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pubmed:abstractText |
Amyotrophic lateral sclerosis (ALS) is an incurable degenerative disorder of motoneurons. We recently reported that reduced expression of Vegfa causes ALS-like motoneuron degeneration in Vegfa(delta/delta) mice. In a meta-analysis of over 900 individuals from Sweden and over 1,000 individuals from Belgium and England, we now report that subjects homozygous with respect to the haplotypes -2,578A/-1,154A/-634G or -2,578A/-1,154G/-634G in the VEGF promoter/leader sequence had a 1.8 times greater risk of ALS (P = 0.00004). These 'at-risk' haplotypes lowered circulating VEGF levels in vivo and reduced VEGF gene transcription, IRES-mediated VEGF expression and translation of a novel large-VEGF isoform (L-VEGF) in vivo. Moreover, SOD1(G93A) mice crossbred with Vegfa(delta/delta) mice died earlier due to more severe motoneuron degeneration. Vegfa(delta/delta) mice were unusually susceptible to persistent paralysis after spinal cord ischemia, and treatment with Vegfa protected mice against ischemic motoneuron death. These findings indicate that VEGF is a modifier of motoneuron degeneration in human ALS and unveil a therapeutic potential of Vegfa for stressed motoneurons in mice.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1061-4036
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pubmed:author |
pubmed-author:AdolfssonRolfR,
pubmed-author:Al-ChalabiAmmarA,
pubmed-author:AndersenPeter MPM,
pubmed-author:AnderssonJörgenJ,
pubmed-author:AwataTakuyaT,
pubmed-author:BeckmanLarsL,
pubmed-author:BornesStephanieS,
pubmed-author:CarmelietPeterP,
pubmed-author:CollenDésiréD,
pubmed-author:Del-FaveroJurgenJ,
pubmed-author:DesmetFrederikF,
pubmed-author:DewerchinMiekeM,
pubmed-author:HansenValerieV,
pubmed-author:KatayamaShigehiroS,
pubmed-author:LambrechtsDietherD,
pubmed-author:Lang-LazdunskiLoïcL,
pubmed-author:LeighNigelN,
pubmed-author:MarklundStefan LSL,
pubmed-author:MoonsLieveL,
pubmed-author:MorimotoMasafumiM,
pubmed-author:MorrisonKaren EKE,
pubmed-author:MussonRhiannonR,
pubmed-author:PallHardev SinghHS,
pubmed-author:PratsHervéH,
pubmed-author:RobberechtWimW,
pubmed-author:RutgeertsPaulP,
pubmed-author:ShawChristopherC,
pubmed-author:StorkebaumErikE,
pubmed-author:ThijsVincentV,
pubmed-author:Van BroeckhovenChristineC,
pubmed-author:VermeireSeverineS,
pubmed-author:VlietinckRobertR,
pubmed-author:WynsSabineS,
pubmed-author:van MarionIngridI
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pubmed:issnType |
Print
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pubmed:volume |
34
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
383-94
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12847526-Aged,
pubmed-meshheading:12847526-Alleles,
pubmed-meshheading:12847526-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:12847526-Animals,
pubmed-meshheading:12847526-Cell Death,
pubmed-meshheading:12847526-Child,
pubmed-meshheading:12847526-Child, Preschool,
pubmed-meshheading:12847526-Endothelial Growth Factors,
pubmed-meshheading:12847526-Female,
pubmed-meshheading:12847526-Genetic Variation,
pubmed-meshheading:12847526-Haplotypes,
pubmed-meshheading:12847526-Humans,
pubmed-meshheading:12847526-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:12847526-Ischemia,
pubmed-meshheading:12847526-Lymphokines,
pubmed-meshheading:12847526-Male,
pubmed-meshheading:12847526-Mice,
pubmed-meshheading:12847526-Mice, Knockout,
pubmed-meshheading:12847526-Mice, Transgenic,
pubmed-meshheading:12847526-Middle Aged,
pubmed-meshheading:12847526-Motor Neurons,
pubmed-meshheading:12847526-Nerve Degeneration,
pubmed-meshheading:12847526-Paralysis,
pubmed-meshheading:12847526-Spinal Cord Ischemia,
pubmed-meshheading:12847526-Sweden,
pubmed-meshheading:12847526-Vascular Endothelial Growth Factor A,
pubmed-meshheading:12847526-Vascular Endothelial Growth Factors
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pubmed:year |
2003
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pubmed:articleTitle |
VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death.
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pubmed:affiliation |
The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology and Department of Neurology, University Hospital Gasthuisberg, KU Leuven, Leuven, B-3000, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Meta-Analysis
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