ACTH-related peptides: receptors and signal transduction systems involved in their neurotrophic and neuroprotective actions

ACTH-related peptides are promising neurotrophic and neuroprotective agents, as demonstrated in many in vivo and in vitro studies. They accelerate nerve repair after injury, improving both sensor and motor function. Furthermore, ACTH-related peptides have neuroprotective properties against cisplatin- and taxol-induced neurotoxicity, they improve neuronal function in animals with neuropathy due to experimental diabetes, and they prevent degeneration of myelinated axons in rats suffering from experimental allergic neuritis, a model of peripheral demyelinating neuropathy. Studies in neuronal cultures have corroborated these clinical observations and serve to investigate the mechanism of action of the ACTH-related peptide effects. This paper reviews both in vitro and in vivo effects and emphasizes the mechanism of action. Recent data on melanotrophic receptors and signal transduction systems will be discussed in this context.