VIP neurotrophism in the central nervous system: multiple effectors and identification of a femtomolar-acting neuroprotective peptide.

Vasoactive intestinal peptide has neurotrophic and growth-regulating properties. As in the case of many neurotrophic molecules, VIP also has neuroprotective properties, including the prevention of cell death associated with excitotoxicity (NMDA), beta-amyloid peptide, and gp120, the neurotoxic envelope protein from the human immunodeficiency virus. The neurotrophic and neuroprotective properties are mediated in part through the action of glial-derived substances released by VIP. These substance include cytokines, protease nexin I, and ADNF, a novel neuroprotective protein with structural similarities to heat-shock protein 60. Antiserum against ADNF produced neuronal cell death and an increase in apoptotic neurons in cell culture. A 14 amino acid peptide (ADNF-14) derived from ADNF has been discovered that mimics the survival-promoting action of the parent protein. These studies support the conclusion that VIP, PACAP, and associated molecules are both important regulators of neurodevelopment and strong candidates for therapeutic development for the treatment of neurodegenerative disease.