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
en 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.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Hipoxia de la Célula
/
Factores de Crecimiento Endotelial
/
Linfocinas
/
Elementos de Respuesta
/
Neuronas Motoras
/
Degeneración Nerviosa
Tipo de estudio:
Etiology_studies
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2001
Tipo del documento:
Article
País de afiliación:
Bélgica