VEGF at the neurovascular interface: therapeutic implications for motor neuron disease.
VEGF was discovered almost 25 years ago, and its angiogenic activity has been extensively studied ever since. Accumulating evidence indicates, however, that VEGF also has direct effects on neuronal cells. VEGF exerts neuroprotective effects on various cultured neurons of the central nervous system. In vivo, VEGF controls the correct migration of facial branchiomotor neurons in the developing hindbrain and stimulates the proliferation of neural stem cells in enriched environments and after cerebral ischemia. Transgenic mice expressing reduced levels of VEGF develop late-onset motor neuron degeneration, reminiscent of amyotrophic lateral sclerosis (ALS), whereas reduced levels of VEGF have been implicated in a polyglutamine-induced model of motor neuron degeneration. Recent data further reveal that intracerebroventricular delivery of recombinant VEGF protein delays disease onset and prolongs survival of ALS rats, whereas intramuscular administration of a VEGF-expressing lentiviral vector increases the life expectancy of ALS mice by as much as 30%. Deciphering the precise role of VEGF at the neurovascular interface promises to uncover new insights into the development and pathology of the nervous system, helpful to design novel strategies to treat (motor) neurodegenerative disorders.
Lambrechts
Diether
D
Center for Transgene Technology and Gene Therapy, Flanders Interuniversitary Institute for Biotechnology, KULeuven, Campus Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium.
Carmeliet
Peter
P
D000690:Amyotrophic Lateral Sclerosis / Q000628:therapy*; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D002490:Central Nervous System / Q000098:blood supply*; D041321:Chromosomes, Human, X; D015316:Genetic Therapy; D006801:Humans; D020104:Immunophilins / Q000235:genetics / Q000502:physiology; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009134:Muscular Atrophy, Spinal / Q000628:therapy; D012259:Ribonuclease, Pancreatic / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use
D043925:Angiogenesis Inducing Agents; D042461:Vascular Endothelial Growth Factor A; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D020104:Immunophilins