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Titolo:
Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration
Autore:
Oosthuyse, B; Moons, L; Storkebaum, E; Beck, H; Nuyens, D; Brusselmans, K; Van Dorpe, J; Hellings, P; Gorselink, M; Heymans, S; Theilmeier, G; Dewerchin, M; Laudenbach, V; Vermylen, P; Raat, H; Acker, T; Vleminckx, V; Van den Bosch, L; Cashman, N; Fujisawa, H; Drost, MR; Sciot, R; Bruyninckx, F; Hicklin, DJ; Ince, C; Gressens, P; Lupu, F; Plate, KH; Robberecht, W; Herbert, JM; Collen, D; Carmeliet, P;
Indirizzi:
Katholieke Univ Leuven, Flanders Interuniv Inst Biotechnol, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium Katholieke Univ Leuven Louvain Belgium B-3000 y, B-3000 Louvain, Belgium FAU Erlangen Nurnberg, Dept Neuropathol, D-91054 Erlangen, Germany FAU Erlangen Nurnberg Erlangen Germany D-91054 D-91054 Erlangen, Germany Katholieke Univ Leuven, Fac Med, B-3000 Louvain, Belgium Katholieke Univ Leuven Louvain Belgium B-3000 d, B-3000 Louvain, Belgium Univ Maastricht, CARIM, NL-6200 MD Maastricht, Netherlands Univ Maastricht Maastricht Netherlands NL-6200 MD aastricht, Netherlands Hop Robert Debre, INSERM E9935, F-75019 Paris, France Hop Robert Debre Paris France F-75019 NSERM E9935, F-75019 Paris, France Hop Robert Debre, Serv Neruol Pediat, F-75019 Paris, France Hop Robert Debre Paris France F-75019 ruol Pediat, F-75019 Paris, France Univ Amsterdam, Dept Anesthesiol, Amsterdam, Netherlands Univ Amsterdam Amsterdam Netherlands nesthesiol, Amsterdam, Netherlands Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON M5S 3H2, Canada UnivToronto Toronto ON Canada M5S 3H2 t Dis, Toronto, ON M5S 3H2, Canada Nagoya Univ, Dept Biol Mol, Nagoya, Aichi 46401, Japan Nagoya Univ NagoyaAichi Japan 46401 Biol Mol, Nagoya, Aichi 46401, Japan ImClone Syst Inc, New York, NY 10014 USA ImClone Syst Inc New York NY USA10014 e Syst Inc, New York, NY 10014 USA Thrombosis Res Inst, Vasc Biol Lab, London SW3 6LR, England Thrombosis ResInst London England SW3 6LR Lab, London SW3 6LR, England
Titolo Testata:
NATURE GENETICS
fascicolo: 2, volume: 28, anno: 2001,
pagine: 131 - 138
SICI:
1061-4036(200106)28:2<131:DOTHEI>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMYOTROPHIC-LATERAL-SCLEROSIS; FACTOR MESSENGER-RNA; SPINAL-CORD; INDUCIBLE FACTOR-1; FACTOR EXPRESSION; NERVOUS-SYSTEM; VEGF; ANGIOGENESIS; ISCHEMIA; MODEL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Carmeliet, P Katholieke Univ Leuven, Flanders Interuniv Inst Biotechnol, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium Katholieke Univ Leuven Louvain Belgium B-3000 vain, Belgium
Citazione:
B. Oosthuyse et al., "Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration", NAT GENET, 28(2), 2001, pp. 131-138

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. Vegf(165) 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 08:14:17