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Title: Therapeutic potential of VEGF and VEGF - derived peptide in peripheral neuropathies
Authors: Verheyen, Ann ×
Peeraer, Eve
Lambrechts, Diether
Poesen, Koen
Carmeliet, Peter
Shibuya, Masabumi
Pintelon, Isabel
Timmermans, Jean-Pierre
Nuydens, Rony
Meert, Theo #
Issue Date: Aug-2013
Publisher: Pergamon Press
Series Title: Neuroscience vol:244 pages:77-89
Article number: S0306-4522(13)00305-9
Abstract: Besides its prominent role in angiogenesis, the vascular endothelial growth factor (VEGF) also exerts important protective effects on neurons. In particular, mice expressing reduced levels of VEGF suffer from late-onset motor neuron degeneration, whereas VEGF delivery significantly delays motor neuron death in ALS mouse models, at least partly through neuroprotective effects. Additionally, VEGF protects dorsal root ganglion (DRG) neurons against paclitaxel-induced neurotoxicity. Here, we demonstrate that VEGF also protects DRG neurons against hyperglycemia-induced neuronal stress as a model of diabetes-induced peripheral neuropathy. Specifically, VEGF decreased expression of the stress-related gene ATF3 in DRG neurons isolated from steptozotocin-induced diabetic mice (ex vivo) and in isolated DRG neurons exposed to high glucose concentrations (in vitro). In vivo, local VEGF application also protected against paclitaxel- and diabetes-induced neuropathies without causing side effects. A small synthetic VEGF mimicking pentadecapeptide (QK) exerted similar effects on DRG cultures: the peptide reduced ATF3 expression in vitro and ex vivo in paclitaxel- and hyperglycemia-induced models of neuropathy to a similar extent as the full-length recombinant VEGF protein. By using transgenic mice selectively overexpressing the VEGF receptor 2 (VEGFR2) in postnatal neurons, these neuroprotective effects were shown to be mediated through VEGF receptor 2. Overall, these results underscore the potential of VEGF and VEGF-derived peptides for the treatment of peripheral neuropathies.
URI: 
ISSN: 0306-4522
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
Department of Neurosciences - miscellaneous
Department of Health and Technology - UC Leuven
× corresponding author
# (joint) last author

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