Protective effects of PACAP in ischemia

Pituitary adenylate cyclase activating polypeptide (PACAP) is an ubiquitous peptide involved, among others, in neurodevelopment, neuromodulation, neuroprotection, neurogenic inflammation and nociception. Presence of PACAP and its specific receptor, PAC1, in the trigeminocervical complex, changes of PACAP levels in migraine patients and the migraine-inducing effect of PACAP injection strongly support the involvement of PACAP/PAC1 receptor in migraine pathogenesis. While antagonizing PAC1 receptor is a promising therapeutic target in migraine, the diverse array of PACAP's functions, including protection in ischemic events, requires that the cost-benefit of such an intervention is well investigated by taking all the beneficial effects of PACAP into account. In the present review we summarize the protective effects of PACAP in ischemia, especially in neuronal ischemic injuries, and discuss possible points to consider when developing strategies in migraine therapy interfering with the PACAP/PAC1 receptor system.