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Hedgehog (Hh) is composed of N-terminal and C-terminal domains that dissociate in a self-catalyzed proteolytic cleavage reaction. The N-terminal product HhNp, modified by cholesterol during self-cleavage, harbors all known Hh signaling activities. When synthesized in the absence of the C-terminal domain (and hence lacking cholesterol modification), the N-terminal domain is aberrantly targeted and released selectively into the retina.
Hedgehog signaling pathway is linked to tumorigenesis and is aberrantly activated in a variety of cancers. Hh ligands bind to and suppress the transmembrane receptor Patched (PTCH), which suppresses Smoothened (SMO), a seven-transmembrane-helix protein that positively regulates the Hh pathway.
Sonic hedgehog (Shh) is a morphogen essential to the developing nervous system that continues to play an important role in adult life by contributing to cell proliferation and differentiation, maintaining blood-brain barrier integrity, and being cytoprotective against oxidative and excitotoxic stress, all features of importance in amyotrophic lateral sclerosis (ALS).
Indian hedgehog (Ihh), a signaling molecule that plays a pivotal role in the regulation of chondrocyte proliferation, maturation, and ossification both in long-bone development and digit joint formation, has also been found to be essential for temporomandibular joint (TMJ) development.
Desert hedgehog (Dhh), one of the Hedgehog family members, is expressed by Schwann cells of peripheral nerves.
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