Multiple Actions of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Schwann Cell Biology

The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) is a well-recognized endogenously produced pleiotropic molecule that elicits a broad range of biological functions in various cell types, including in Schwann cells (SCs). Its main actions, which have been primarily associated to neuroprotection both in the central and peripheral nervous system (CNS and PNS), are currently being extended, and new intriguing roles in regulating several aspects of CNS and PNS physiology are emerging. The overall goal of the present chapteris to provide an update of the recent advances that have been made to elucidate the multiple actions elicited by PACAP in relationship to the complex biology of SCs, whose seminal role is to provide myelin ensheathment to nerve fibers forming peripheral nerves. After reviewing the main functions of this specific type of neuroglia, a major goal will be to describe PACAP regulatory roles in several biological processes in SCs, including myelin generation, cell protection against injury and its secretagogue activity on proteolytic enzymes. Furthermore, a discussion on the impact that PACAP-mediated changes may have on peripheral axonal myelination and repair processes after nerve injury will be opened. The final aim will be to illustrate the potential benefits of PACAP treatment in chronic pain. In this section, particular attention will be given to those findings inferring on SCs involvement in the development of neuropathic pain and the key modulatory role elicited by PACAP. The contents herein summarized could offer a new perspective of PACAP to aid in the future development of more stable peptide analogues in the scenario of peripheral neuropathies and provide a comprehensive tool that will help to dissect novel PACAP-regulated functions in SCs.