Class II G protein-coupled receptors and their ligands in neuronal function and protection.
G protein-coupled receptors (GPCRs) play pivotal roles in regulating the function and plasticity of neuronal circuits in the nervous system. Among the myriad of GPCRs expressed in neural cells, class II GPCRs which couples predominantly to the Gs-adenylate cyclase-cAMP signaling pathway, have recently received considerable attention for their involvement in regulating neuronal survival. Neuropeptides that activate class II GPCRs include secretin, glucagon-like peptides (GLP-1 and GLP-2), growth hormone-releasing hormone (GHRH), pituitary adenylate cyclase activating peptide (PACAP), corticotropin-releasing hormone (CRH), vasoactive intestinal peptide (VIP), parathyroid hormone (PTH), and calcitonin-related peptides. Studies of patients and animal and cell culture models, have revealed possible roles for class II GPCRs signaling in the pathogenesis of several prominent neurodegenerative conditions including stroke, Alzheimer's, Parkinson's, and Huntington's diseases. Many of the peptides that activate class II GPCRs promote neuron survival by increasing the resistance of the cells to oxidative, metabolic, and excitotoxic injury. A better understanding of the cellular and molecular mechanisms by which class II GPCRs signaling modulates neuronal survival and plasticity will likely lead to novel therapeutic interventions for neurodegenerative disorders.
Martin
Bronwen
B
Laboratory of Neurosciences, National Institute on Ageing Intramural Research Program, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Lopez de Maturana
Rakel
R
Brenneman
Randall
R
Walent
Tom
T
Mattson
Mark P
MP
Maudsley
Stuart
S
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism*; D019610:Cytoprotection / Q000502:physiology*; D006801:Humans; D008024:Ligands; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D008024:Ligands; D009479:Neuropeptides; D043562:Receptors, G-Protein-Coupled