Vascular and Neuronal Effects of VEGF in the Nervous System

Blood vessels and nerves are both vital channels to and from tissues. Recent genetic insights show that they have much more in common than was originally anticipated. They use similar signals and principles to differentiate, grow, and navigate toward their targets. Moreover, the vascular and nervous systems cross talk and, when dysregulated, this contributes to medically important diseases. No factor is better known for its angiogenic effects than vascular endothelial growth factor (VEGF)—this molecule has been implicated in virtually every type of angiogenic disorder, including those associated with cancer, ischemia, and inflammation. Recent studies revealed, however, that VEGF is also involved in neurodegeneration. The role of VEGF in the nervous system is not restricted only to regulating vessel growth: VEGF also has direct effects on different types of neural cells—including even neural stem cells. Furthermore, genetic studies showed that mice with reduced VEGF levels develop adult-onset motor neuron degeneration reminiscent of the human neurodegenerative disorder amyotrophic lateral sclerosis (ALS), and additional genetic studies confirmed that VEGF is a modifier of motor neuron degeneration in humans and in SOD1G93A mice—a model of ALS. Reduced VEGF levels may promote motor neuron degeneration by limiting neural tissue perfusion, by reducing VEGF-dependent neuroprotection and/or by influencing neuroregeneration/neurogenesis. VEGF also affects neuron survival after acute spinal cord or cerebral ischemia and has been implicated in other neurological disorders such as diabetic and ischemic neuropathy, nerve regeneration, Parkinson's disease, Alzheimer's disease, and multiple sclerosis. These findings offer novel opportunities to better decipher the insufficiently understood molecular pathogenesis of many neurodegenerative disorders, and promise to open new avenues for future improved treatment.