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Novel role for Vascular Endothelial Growth Factor (VEGF) Receptor-1 and it's ligand VEGF-B in Motor Neuron Degeneration

09/03/2010 - Atualizado em 07/03/2013

Although vascular endothelial growth factor-B (VEGF-B) is a homolog of the angiogenic factor VEGF, it has only minimal angiogenic activity, raising the question of whether this factor has other (more relevant) biological properties. Intrigued by the possibility that VEGF family members affect neuronal cells, we explored whether VEGF-B might have a role in the nervous system. Here, we document that the 60 kDa VEGF-B isoform, VEGF-B186, is a neuroprotective factor. VEGF-B186 protected cultured primary motor neurons against degeneration. Mice lacking VEGF-B also developed a more severe form of motor neuron degeneration when intercrossed with mutant SOD1 mice.

The in vitro and in vivo effects of VEGF-B186 were dependent on the tyrosine kinase activities of its receptor, Flt1, in motor neurons. When delivered intracerebroventricularly, VEGF-B186 prolonged the survival of mutant SOD1 rats. Compared with a similar dose of VEGF, VEGF-B186 was safer and did not cause vessel growth or blood?brain barrier leakiness. The neuroprotective activity of VEGF-B, in combination with its negligible angiogenic/permeability activity, offers attractive opportunities for the treatment of neurodegenerative diseases.

Autors: Poesen, Koen; Lambrechts, Diether; Damme, Philips Van; Dhondt, Joke; Bender, Florian; Frank, Nicolas; Bogaert, Elke; Claes, Bart; Heylen, Line; Verheyen, An; Raes, Katrien; Tjwa, Marc; Eriksson, Ulf; Shibuya, Masabumi; Nuydens, Rony; Bosch, Ludo Van Den; Meert, Theo; D'Hooge, Rudi; Sendtner, Michael; Robberecht, Wim; Carmeliet, Peter.



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