Sonic Hedgehog signaling and potential therapeutic indications

Sonic hedgehog (Shh) is a glycoprotein molecule that is expressed throughout the central nervous system (CNS). It is important during neurodevelopment, particularly through its induction of endogenous neural precursor cells and neural stem cells. The signaling system by which Shh has its diffuse effects on multiple end organs depends on a downstream signaling cascade initiated by binding to the receptor Patched (PTC) on Shh-specific target cells. The downstream signaling cascade has widespread effects on multiple organ systems. Research into tumor suppressive effects and germline mutations has uncovered important implications in neuro-oncology. Modulating the neuroproliferative effects of the Shh signaling cascade implicated a potential role in ameliorating the effects of CNS injury, particularly in animal models of spinal cord injury and cerebral cortical ischemia. This chapter provides a summary of the Shh signaling mechanism and a review of its impact in these neurological disorders.