Medline/PubMed Citation | Related Articles in PubMed | Download to Citation Manager

ASN NEURO (2011) 3(4):art:e00065.doi:10.1042/AN20110024

Enhanced Full Text

PDF

Legacy HTML

Send to a friend

Add a comment

Citing articles

Review

Targeting VIP and PACAP receptor signalling: new therapeutic strategies in multiple sclerosis

Yossan‑Var Tan and James A Waschek¹

The Semel Institute and Department of Psychiatry, the David Geffen School of Medicine, University of California, Los Angeles, CA 90095, U.S.A.

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.

Key words: autoimmunity, drug-design, experimental autoimmune encephalomyelitis (EAE), neuroprotection, PACAP, VIP

Abbreviations: AC, adenylate cyclase, AD, Alzheimer's disease, ADNF, activity-dependent neurotrophic factor, ADNP, activity-dependent neuroprotective protein, APC, antigen-presenting cells, BM, bone marrow, Bz-Phe, benzophenone-Phe, CCR, CC chemokine receptor,, CIA, collagen-induced arthritis, CNS, central nervous system, DC, dendritic cell, DMD, disease-modifying drug, DSS, dextran sodium sulfate, EAE, experimental autoimmune encephalomyelitis, FDA, Food and Drug Administration, GPCR, G-protein-coupled receptor, IFN, interferon, IL-6, interleukin 6, JNK, c-Jun N-terminal kinase, KO, knockout, LPS, lipopolysaccharide, MAPK, mitogen-activated protein kinase, MCP-1, monocyte chemoattractant protein 1, MIP-2, macrophage inflammatory protein 2, MOG, myelin oligodendrocyte glycoprotein, MS, multiple sclerosis, MSC, mesenchymal stem cell, NAP, neutrophil-activating protein, NMDA, N-methyl-d-aspartate, PACAP, pituitary adenylate cyclase-activating peptide, PKA, protein kinase A, PKC, protein kinase C, PLC, phospholipase C, PMCAO, permanent middle cerebral artery occlusion, PPMS, primary progressive form of MS, RAMP, receptor-activity-modifying protein, RANTES, regulated upon activation, normal T-cell expressed and secreted, SAPK, stress-activated protein kinase, SCG, superior cervical ganglion, SPMS, secondary progressive form of MS, S-SCAM, synaptic scaffolding molecule, STAT, signal transducer and activator of transcription, TGFβ, transforming growth factor β, TM, transmembrane, TNFα, tumour necrosis factor α, Treg, regulatory T, VIP, vasoactive intestinal peptide, WT, wild-type

¹To whom correspondence should be addressed (email JWaschek@mednet.ucla.edu).

Received 9 August 2011; accepted 7 September 2011

Published as ASN NEURO Immediate Publication 7 September 2011, doi:10.1042/AN20110024

©2011 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.