The Hedgehog signaling pathway – implications for drug targets in cancer and neurodegenerative disorders

Abstract

The Hedgehog (Hh) pathway is a highly conserved signaling cascade involved in many developmental processes. Among others, these include patterning of the ventral neural tube and establishment of left–right asymmetry of the embryo. Additionally, the pathway regulates the development of numerous tissues and cell types. Mutations in elements of the pathway are associated with congenital diseases and defects, and ectopic Hh signaling activity is implicated in the development of a number of neoplasms. While little is known of Hh signaling function in the adult organism, a role of the pathway in maintenance of adult organs and cell types, including several neuronal subtypes in the central nervous system, is beginning to emerge. Elements of the Hh pathway are therefore potential drug targets for the treatment of cancers and degenerative diseases like Parkinson’s disease, and the recent isolation of synthetic molecules capable of modulating the activity of the Hh cascade through a direct interaction with elements of the pathway is promising.