Are anti-angiogenic drugs useful in neurodegenerative disorders?

Recently, a pivotal role for neuroinflammation in the pathogenesis of several neurodegenerative diseases has been recognized. Once activated, glial cells produce pathological amounts of neurotoxic substances driving neurodegeneration into chronic progression through a self-propagating cycle. Nevertheless, mounting evidence suggests that also angiogenesis may importantly contribute to neurodegeneration, since activated glial cells may release also pro-angiogenic factors. A deregulation of the balance between pro- and anti-angiogenic mediators has been reported in in vivo and in vitro models of neuroinflammation. Indeed, in Alzheimer's disease brain, a significant increase in the expression of pro-angiogenic growth factors, such as vascular endothelial growth factor, was found strictly co-localized with senile plaques. In addition, converging results indicate that thalidomide and its derivatives, having newly discovered anti-inflammatory and anti-angiogenic properties, are useful in the prevention of several hallmarks of neurodegeneration occurring in experimental models of Parkinson's and Alzheimer's diseases. The present review primarily discusses about the possible roles, still under debate, of angiogenesis in neurodegeneration, and focuses on the identification of new possible anti-angiogenic compounds that could open new horizons in the treatment of neurodegenerative diseases where angiogenesis is detrimental.