Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration.
Nat Genet
; 28(2): 131-8, 2001 Jun.
Article
em En
| MEDLINE
| ID: mdl-11381259
ABSTRACT
Hypoxia stimulates angiogenesis through the binding of hypoxia-inducible factors to the hypoxia-response element in the vascular endothelial growth factor (Vegf) promotor. Here, we report that deletion of the hypoxia-response element in the Vegf promotor reduced hypoxic Vegf expression in the spinal cord and caused adult-onset progressive motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis. The neurodegeneration seemed to be due to reduced neural vascular perfusion. In addition, Vegf165 promoted survival of motor neurons during hypoxia through binding to Vegf receptor 2 and neuropilin 1. Acute ischemia is known to cause nonselective neuronal death. Our results indicate that chronic vascular insufficiency and, possibly, insufficient Vegf-dependent neuroprotection lead to the select degeneration of motor neurons.
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Base de dados:
MEDLINE
Assunto principal:
Hipóxia Celular
/
Fatores de Crescimento Endotelial
/
Linfocinas
/
Elementos de Resposta
/
Neurônios Motores
/
Degeneração Neural
Tipo de estudo:
Etiology_studies
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article