Therapeutic potential of VEGF and VEGF-derived peptide in peripheral neuropathies

Autor: Masabumi Shibuya, Koen Poesen, Peter Carmeliet, Jean-Pierre Timmermans, Rony Nuydens, Eve Peeraer, Theo Meert, Diether Lambrechts, Ann Verheyen, Isabel Pintelon
Rok vydání: 2013
Předmět:
Male
Vascular Endothelial Growth Factor A
peripheral neuropathy
Angiogenesis
Drug Evaluation
Preclinical
ANGIOGENESIS
Mice
chemistry.chemical_compound
Dorsal root ganglion
Ganglia
Spinal
RAT MODEL
IN-VIVO
General Neuroscience
Peripheral Nervous System Diseases
VEGF
peptide
Vascular endothelial growth factor
Neuroprotective Agents
medicine.anatomical_structure
DIABETIC-NEUROPATHY
STIMULATES AXONAL OUTGROWTH
Life Sciences & Biomedicine
VASCULAR-PERMEABILITY FACTOR
Paclitaxel
Mice
Transgenic
GENE-TRANSFER
Neuroprotection
Diabetes Mellitus
Experimental
medicine
Animals
ATF3
Activating Transcription Factor 3
Science & Technology
business.industry
Neurosciences
Neurotoxicity
Motor neuron
medicine.disease
Vascular Endothelial Growth Factor Receptor-2
Peptide Fragments
NERVOUS-SYSTEM
Rats
Glucose
nervous system
chemistry
ENDOTHELIAL GROWTH-FACTOR
Immunology
Cancer research
Neurosciences & Neurology
Human medicine
business
Ex vivo
NEUROTROPHIC FACTOR
Zdroj: Neuroscience
ISSN: 0306-4522
Popis: 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 activating transcription factor 3 (ATF3) in DRG neurons isolated from streptozotocin-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 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. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
Databáze: OpenAIRE
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