Neuroprotective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide

Pituitary adenylate cyclase-activating polypeptide (PACAP) was first isolated from an ovine hypothalamus by Dr. Arimura and his colleagues in 1989 and demonstrated to be one of most conserved peptide through the different species. PACAP belongs to the secretin/glucagon/vasoactive intestinal peptide family and exists in a full form (PACAP-38) and a shorter form (PACAP-27). PACAP and its three different receptors, PAC1, VPAC1 andVPAC2, have been demonstrated in the central and peripheral nervous system. Furthermore, previous studies have proved that PACAP has pleiotropic functions, such as the regulation of neurodevelopment and protection against neuron apoptosis. The peptide exerts its physiological effects via PAC1, VPAC1 and VPAC2 receptors, which all belong to the class B, family of G protein-coupled receptors (GPCRs). The primary signaling pathways of PACAP receptors are cAMP mediated both PKA and MAPK pathways. The phospholipase D (PLD) and calcium signaling pathways can be activated by PACAP receptors as well.

Evidences from numbers of in vitro and in vivo experiments suggest that PACAP may enhance neuronal survival and neuronalregeneration in the nervous system. The cultured cerebellar granule cell, a model of programmed cell death, is widely used for investigation of the neuroprotective factors.