More Than Three Decades After Discovery of the Neuroprotective Effect of PACAP, What Is Still Preventing Its Clinical Use?

Discovered in 1989, pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with strong neuroprotective properties, as shown in various neurodegenerative preclinical models of Parkinson, Alzheimer, or Huntington diseases. PACAP neuroprotection has also been reported in animal models of cerebral ischemia and traumatic brain injury. The neuroprotective effect of PACAP occurs through its capacity to modulate most of the multiphasic aspects of neuronal diseases, such as oxidative stress, neuronal cell death, and inflammation. However, more than three decades after its discovery, and although PACAP neurotrophic and neuroprotective activities have now been largely documented, its clinical use is still awaited. Thus, the aim of this manuscript is to discuss the main reasons which limit the use of PACAP as a therapeutic agent for the treatment of neuronal diseases. To achieve this objective, an opinion survey has been conducted among experts in the field of PACAP, and a bibliographic investigation was carried out.