title: Targeting VIP and PACAP receptor signalling: new therapeutic strategies in multiple sclerosis.
abstract: MS (multiple sclerosis) is a chronic autoimmune and neurodegenerative pathology of the CNS (central nervous system) affecting approx. 2.5 million people worldwide. Current and emerging DMDs (disease-modifying drugs) predominantly target the immune system. These therapeutic agents slow progression and reduce severity at early stages of MS, but show little activity on the neurodegenerative component of the disease. As the latter determines permanent disability, there is a critical need to pursue alternative modalities. VIP (vasoactive intestinal peptide) and PACAP (pituitary adenylate cyclase-activating peptide) have potent anti-inflammatory and neuroprotective actions, and have shown significant activity in animal inflammatory disease models including the EAE (experimental autoimmune encephalomyelitis) MS model. Thus, their receptors have become candidate targets for inflammatory diseases. Here, we will discuss the immunomodulatory and neuroprotective actions of VIP and PACAP and their signalling pathways, and then extensively review the structure-activity relationship data and biophysical interaction studies of these peptides with their cognate receptors.
authors: The Semel Institute, Department of Psychiatry, the David Geffen School of Medicine, University of California, Los Angeles, 90095, USA.
authors: Yossan-Var
authors: YV
authors: Tan
authors: James A
authors: JA
authors: Waschek
mesh_terms: D000818:Animals; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000378:metabolism / Q000628:therapy*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D007155:Immunologic Factors; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide