Pharmacological Manipulation of Neural Progenitor Pathways In Situ: Possibilities for Neural Restoration in the Injured Adult Brain

Progress over the last decade has confirmed the occurrence of de novo neurogenesis within discrete regions of the adult brain. It has been demonstrated that under certain conditions neurogenesis can be stimulated above basal levels in the adult, and that resident pools of adult progenitors can be manipulated to generate new neurons in situ. Undoubtedly, these reports prelude possibilities for applications in regenerative medicine. Much attention is now being focused on the elucidation of the discrete mechanisms that are involved in the induction of the neurogenic response in the adult brain and whether these pathways can be pharmacologically manipulated to endogenously replace lost cells and alleviate neuropathy. There is evidence that the re-expression of many key molecular components of the various pathways controlling cellular proliferation, migration and differentiation during development can be re-induced within the mature brain. Recent reports show that the expression of a number of these developmentally-associated molecules occurs in close association with adult progenitor proliferation and neurogenesis, signifying an additional role for these systems in eliciting the adult neurogenic response. Here we review the literature regarding this phenomenon, with reference to the main candidate pathways involved including bone morphogenetic protein, sonic hedgehog and Wnt signalling pathways, and discuss the progress which has been made in the use of small molecules to manipulate these pathways and affect adult neurogenesis in situ.