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Title: Novel Role for Vascular Endothelial Growth Factor (VEGF) Receptor-1 and Its Ligand VEGF-B in Motor Neuron Degeneration
Authors: Poesen, Koen *
Lambrechts, Diether *
Van Damme, Philip
Dhondt, Joke
Bender, Florian
Frank, Nicolas
Bogaert, Elke
Claes, Bart
Heylen, Line
Verheyen, An
Raes, Katrien
Tjwa, Marc
Eriksson, Ulf
Shibuya, Masabumi
Nuydens, Rony
Van Den Bosch, Ludo
Meert, Theo
D'Hooge, Rudi
Sendtner, Michael
Robberecht, Wim
Carmeliet, Peter # ×
Issue Date: Oct-2008
Publisher: The Society for Neuroscience
Series Title: Journal of Neuroscience vol:28 issue:42 pages:10451-10459
Abstract: 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-B(186), is a neuroprotective factor. VEGF-B(186) 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-B(186) were dependent on the tyrosine kinase activities of its receptor, Flt1, in motor neurons. When delivered intracerebroventricularly, VEGF-B(186) prolonged the survival of mutant SOD1 rats. Compared with a similar dose of VEGF, VEGF-B(186) 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.
URI: 
ISSN: 0270-6474
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Biological Psychology
Vesalius Research Centre (-)
Research Group Experimental Neurology
Laboratory for Neurobiology (Vesalius Research Center)
Molecular and Vascular Biology
Laboratory of Translational Genetics (Vesalius Research Center) (+)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
* (joint) first author
× corresponding author
# (joint) last author

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