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Neuroprotective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide

Rui Ji, Lingbin Meng and Rongqiang Yang

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the secretin/glucagon/vasoactive intestinal peptide (VIP) super family. PACAP was first isolated from an ovine hypothalamus and named because it stimulated cAMP production in the rat pituitary cell culture. PACAP is widely expressed in the central and peripheral nervous systems. PACAP plays the roles of neurotransmitter, neuromodulator and neurotrophic factors via three Gprotein binding receptors, PAC1, VAPC1 and VPAC2. A number of recent studies have discovered the neuroprotective functions of PACAP in both in vitro and in vivo models. PACAP protects the neurons from death through both direct and indirect ways. PACAP inhibits caspase-3 through cAMP-PKA or MAP kinase-signaling pathways. Moreover, PACAP can stimulate astrocytes to release neuroprotective factors, such as interleukin-6 (IL-6). The present review will briefly summarize the recent studies and provide information for the future use in the clinic.