G protein-coupled receptor; GPR173; GPR27; GPR85; SREB family; autism; schizophrenia; super-conserved receptors; Drug Discovery; Pharmacology; Molecular Medicine
Abstract :
[en] The super-conserved receptors expressed in the brain (SREB) constitute a family of orphan G protein-coupled receptors that include GPR27 (SREB1), GPR85 (SREB2) and GPR173 (SREB3). Their sequences are highly conserved in vertebrates, and they are almost exclusively expressed in the central nervous system. This family of receptors has attracted much attention due to their putative physiological functions and their potential as novel drug targets. The SREB family has been postulated to play important roles in a wide range of different diseases, including pancreatic β-cell insulin secretion and regulation, schizophrenia, autism and atherosclerosis. This review intends to provide a comprehensive overview of the SREB family and its recent advances in biology and medicinal chemistry. [en] In recent years, the super-conserved receptors expressed in the brain called GPR27, GPR85 and GPR173 have attracted much interest in the field of medicinal science. They have one important feature in common: they are all almost entirely found in the brain. Researchers have investigated their functions in the body in various animal models, as well as their utility in future drug development. GPR27 has been found to be involved in insulin and blood sugar processes in the body and therefore may be important for diabetes treatment. GPR85 is thought to be linked to brain diseases such as schizophrenia and autism. GPR173 is linked to many different illnesses, including atherosclerosis (the buildup of fats, cholesterol and other substances in arteries) and Type 2 diabetes.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Bayrak, Alp ; Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry & Tübingen Center for Academic Drug Discovery (TüCAD2) Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
Hanson, Julien ; Université de Liège - ULiège > GIGA > GIGA Molecular Biology of Diseases - Molecular Pharmacology
Laufer, Stefan ; Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry & Tübingen Center for Academic Drug Discovery (TüCAD2) Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
Pillaiyar, Thanigaimalai ; Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry & Tübingen Center for Academic Drug Discovery (TüCAD2) Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany
Language :
English
Title :
Super-conserved receptors expressed in the brain: biology and medicinal chemistry efforts.
Huang Y, Todd N, Thathiah A. The role of GPCRs in neurodegenerative diseases: avenues for therapeutic intervention. Curr. Opin. Pharmacol. 32, 96-110 (2017).
Harmar AJ, Hills RA, Rosser EM et al. IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Nucleic Acids Res. 37(Suppl. 1), S680-S685 (2009).
Azam S, Haque M, Jakaria M, Jo SH, Kim IS, Choi DK. G-protein-coupled receptors in CNS: a potential therapeutic target for intervention in neurodegenerative disorders and associated cognitive deficits. Cells 9(2), 506 (2020).
Breton TS, Sampson WGB, Clifford B et al. Characterization of the G protein-coupled receptor family SREB across fish evolution. Sci. Rep. 11(1), 12066 (2021).
Fredriksson R, Schiöth HB. The repertoire of G-protein-coupled receptors in fully sequenced genomes. Mol. Pharmacol. 67(5), 1414-1425 (2005).
Hauser AS, Attwood MM, Rask-Andersen M, Schiöth HB, Gloriam DE. Trends in GPCR drug discovery: new agents, targets and indications. Nat. Rev. Drug Discov. 16(12), 829-842 (2017).
Chopra DG, Yiv N, Hennings TG, Zhang Y, Ku GM. Deletion of Gpr27 in vivo reduces insulin mRNA but does not result in diabetes. Sci. Rep. 10(1), 5629 (2020).
Pillaiyar T, Rosato F, Wozniak M et al. Structure-activity relationships of agonists for the orphan G protein-coupled receptor GPR27. Eur. J. Med. Chem. 225, 113777 (2021).
Yang D, Zhou Q, Labroska V et al. G protein-coupled receptors: structure-and function-based drug discovery. Signal Transduct. Target. Ther. 6(1), 7 (2021).
Chung S, Funakoshi T, Civelli O. Orphan GPCR research. Br. J. Pharmacol. 153(Suppl. 1), S339-S346 (2008).
Laschet C, Dupuis N, Hanson J. The G protein-coupled receptors deorphanization landscape. Biochem. Pharmacol. 153, 62-74 (2018).
Matsumoto M, Saito T, Takasaki J et al. An evolutionarily conserved G-protein coupled receptor family, SREB, expressed in the central nervous system. Biochem. Biophys. Res. Commun. 272(2), 576-582 (2000).
Regard JB, Sato IT, Coughlin SR. Anatomical profiling of G protein-coupled receptor expression. Cell 135(3), 561-571 (2008).
Hellebrand S, Wittenberger T, Schaller HC, Hermans-Borgmeyer I. Gpr85, a novel member of the G-protein coupled receptor family, prominently expressed in the developing mouse cerebral cortex. Brain Res. Gene Expr. Patterns 1(1), 13-16 (2001).
Breton TS, Berlinsky DL. Characterizing ovarian gene expression during oocyte growth in Atlantic cod (Gadus morhua). Comp. Biochem. Physiol. D 9, 1-10 (2014).
Ku GM, Kim H, Vaughn IW et al. Research resource: RNA-seq reveals unique features of the pancreatic cell transcriptome. Mol. Endocrinol. 26(10), 1783-1792 (2012).
Ku GM, Pappalardo Z, Luo CC, German MS, McManus MT. An siRNA screen in pancreatic beta cells reveals a role for Gpr27 in insulin production. PLoS Genet. 8(1), e1002449 (2012).
Matsumoto M, Beltaifa S, Weickert CS et al. A conserved mRNA expression profile of SREB2 (GPR85) in adult human, monkey, and rat forebrain. Brain Res. Mol. Brain Res. 138(1), 58-69 (2005).
Regard JB, Kataoka H, Cano DA et al. Probing cell type-specific functions of Gi in vivo identifies GPCR regulators of insulin secretion. J. Clin. Invest. 117(12), 4034-4043 (2007).
Nath AK, Ma J, Chen ZZ et al. Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish. FASEB J. 34(1), 1546-1557 (2020).
Martin AL, Steurer MA, Aronstam RS. Constitutive activity among orphan class-A G protein coupled receptors. PLoS One 10(9), e0138463 (2015).
Yanai T, Kurosawa A, Nikaido Y et al. Identification and molecular docking studies for novel inverse agonists of SREB, super conserved receptor expressed in brain. Genes Cells 21(7), 717-727 (2016).
Dupuis N, Laschet C, Franssen D et al. Activation of the orphan G protein-coupled receptor GPR27 by surrogate ligands promotes arrestin 2 recruitment. Mol. Pharmacol. 91(6), 595-608 (2017).
Lu S, Jang W, Inoue A, Lambert NA. Constitutive G protein coupling profiles of understudied orphan GPCRs. PLoS One 16(4), e0247743 (2021).
Spaeth JM, Gupte M, Perelis M et al. Defining a novel role for the Pdx1 transcription factor in islet cell maturation and proliferation during weaning. Diabetes 66(11), 2830-2839 (2017).
Jain S, Ruiz De Azua I, Lu H, White MF, Guettier JM, Wess J. Chronic activation of a designer G(q)-coupled receptor improves cell function. J. Clin. Invest. 123(4), 1750-1762 (2013).
Dickinson ME, Flenniken AM, Ji X et al. High-throughput discovery of novel developmental phenotypes. Nature 537(7621), 508-514 (2016).
Hossain S, Mineno K, Katafuchi T. Neuronal orphan G-protein coupled receptor proteins mediate plasmalogens-induced activation of ERK and Akt signaling. PLoS One 11(3), e0150846 (2016).
Dolanc D, Zorec TM, Smole Z et al. The activation of GPR27 increases cytosolic L-lactate in 3T3 embryonic cells and astrocytes. Cells 11(6), 1009 (2022).
Sakai A, Yasui T, Watanave M et al. Development of novel potent ligands for GPR85, an orphan G protein-coupled receptor expressed in the brain. Genes Cells doi: 10. 1111/gtc. 12931 (2022).
Hellebrand S, Schaller HC, Wittenberger T. The brain-specific G-protein coupled receptor GPR85 with identical protein sequence in man and mouse maps to human chromosome 7q31. Biochim. Biophys. Acta 1493(1-2), 269-272 (2000).
Jeon J, Kim C, Sun W, Chung H, Park SH, Kim H. Cloning and localization of rgpr85 encoding rat G-protein-coupled receptor. Biochem. Biophys. Res. Commun. 298(4), 613-618 (2002).
Abrous DN, Koehl M, Le Moal M. Adult neurogenesis: from precursors to network and physiology. Physiol. Rev. 85(2), 523-569 (2005).
Aimone JB, Wiles J, Gage FH. Computational influence of adult neurogenesis on memory encoding. Neuron 61(2), 187-202 (2009).
Ehninger D, Kempermann G. Neurogenesis in the adult hippocampus. Cell Tissue Res. 331(1), 243-250 (2008).
Geuze E, Vermetten E, Bremner JD. MR-based in vivo hippocampal volumetrics: 2. Findings in neuropsychiatric disorders. Mol. Psychiatry 10(2), 160-184 (2005).
Lucassen PJ, Heine VM, Muller MB et al. Stress, depression and hippocampal apoptosis. CNS Neurol. Disord. Drug Targets 5(5), 531-546 (2006).
Trikalinos TA, Karvouni A, Zintzaras E et al. A heterogeneity-based genome search meta-analysis for autism-spectrum disorders. Mol. Psychiatry 11(1), 29-36 (2006).
Voineagu I, Wang X, Johnston P et al. Transcriptomic analysis of autistic brain reveals convergent molecular pathology. Nature 474(7351), 380-384 (2011).
Anney RJ, Lasky-Su J, O'dúshláine C et al. Conduct disorder and ADHD: evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study. Am. J. Med. Genet. B Neuropsychiatr. Genet. 147b(8), 1369-1378 (2008).
Patel C, Cooper-Charles L, McMullan DJ, Walker JM, Davison V, Morton J. Translocation breakpoint at 7q31 associated with tics: further evidence for IMMP2L as a candidate gene for Tourette syndrome. Eur. J. Hum. Genet. 19(6), 634-639 (2011).
Jelén F, Oleksy A, Smietana K, Otlewski J. PDZ domains-common players in the cell signaling. Acta Biochim. Pol. 50(4), 985-1017 (2003).
Fujita-Jimbo E, Tanabe Y, Yu Z et al. The association of GPR85 with PSD-95-neuroligin complex and autism spectrum disorder: a molecular analysis. Mol. Autism 6, 17 (2015).
Radulescu E, Sambataro F, Mattay VS et al. Effect of schizophrenia risk-associated alleles in SREB2 (GPR85) on functional MRI phenotypes in healthy volunteers. Neuropsychopharmacology 38(2), 341-349 (2013).
Hamann S. Sex differences in the responses of the human amygdala. Neuroscientist 11(4), 288-293 (2005).
Mackiewicz KL, Sarinopoulos I, Cleven KL, Nitschke JB. The effect of anticipation and the specificity of sex differences for amygdala and hippocampus function in emotional memory. Proc. Natl Acad. Sci. USA 103(38), 14200-14205 (2006).
Andreano JM, Cahill L. Sex influences on the neurobiology of learning and memory. Learn. Mem. 16(4), 248-266 (2009).
Abel KM, Drake R, Goldstein JM. Sex differences in schizophrenia. Int. Rev. Psychiatry 22(5), 417-428 (2010).
Chen Q, Kogan JH, Gross AK et al. SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory. Eur. J. Neurosci. 36(5), 2597-2608 (2012).
Matsumoto M, Straub RE, Marenco S et al. The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia. Proc. Natl. Acad. Sci. USA. 105(16), 6133-6138 (2008).
Wei X, Lin H, Zhang B et al. Phoenixin-20 prevents ox-LDL-induced attachment of monocytes to human aortic endothelial cells (HAECs): a protective implication in atherosclerosis. ACS Chem. Neurosci. 12(6), 990-997 (2021).
Wang J, Zheng B, Yang S, Tang X, Wang J, Wei D. The protective effects of phoenixin-14 against lipopolysaccharide-induced inflammation and inflammasome activation in astrocytes. Inflamm. Res. 69(8), 779-787 (2020).
Yang Y, Lv Y, Liu J, Zhang S, Li Y, Shi Y. Phoenixin 20 promotes neuronal mitochondrial biogenesis via CREB-PGC-1 pathway. J. Mol. Histol. 51(2), 173-181 (2020).
Sun G, Ren Q, Bai L, Zhang L. Phoenixin-20 suppresses lipopolysaccharide-induced inflammation in dental pulp cells. Chem. Biol. Interact. 318, 108971 (2020).
Nguyen XP, Nakamura T, Osuka S et al. Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis. Reproduction 158(1), 25-34 (2019).
Schalla MA, Stengel A. Phoenixin-a pleiotropic gut-brain peptide. Int. J. Mol. Sci. 19(6), 1726 (2018).
Rajeswari JJ, Unniappan S. Phoenixin-20 stimulates mRNAs encoding hypothalamo-pituitary-gonadal hormones, is pro-vitellogenic, and promotes oocyte maturation in zebrafish. Sci. Rep. 10(1), 6264 (2020).
Yosten GL, Lyu RM, Hsueh AJ et al. A novel reproductive peptide, phoenixin. J. Neuroendocrinol. 25(2), 206-215 (2013).
Lyu RM, Huang XF, Zhang Y et al. Phoenixin: a novel peptide in rodent sensory ganglia. Neuroscience 250, 622-631 (2013).
Treen AK, Luo V, Belsham DD. Phoenixin activates immortalized GnRH and kisspeptin neurons through the novel receptor GPR173. Mol. Endocrinol. 30(8), 872-888 (2016).
Stein LM, Tullock CW, Mathews SK et al. Hypothalamic action of phoenixin to control reproductive hormone secretion in females: importance of the orphan G protein-coupled receptor Gpr173. Am. J. Physiol. Regul. Integr. Comp. Physiol. 311(3), R489-R496 (2016).
Ceriani R, Calfún C, Whitlock KE. Phoenixin(smim20), a gene coding for a novel reproductive ligand, is expressed in the brain of adult zebrafish. Gene Expr. Patterns 39, 119164 (2021).
Kalamon N, Blaszczyk K, Szlaga A et al. Levels of the neuropeptide phoenixin-14 and its receptor GRP173 in the hypothalamus, ovary and periovarian adipose tissue in rat model of polycystic ovary syndrome. Biochem. Biophys. Res. Commun. 528(4), 628-635 (2020).
Kulinska KI, Andrusiewicz M, Dera-Szymanowska A et al. Phoenixin as a new target in the development of strategies for endometriosis diagnosis and treatment. Biomedicines 9(10), 1427 (2021).
Gasparini S, Stein LM, Loewen SP et al. Novel regulator of vasopressin secretion: phoenixin. Am J Physiol Regul Integr Comp Physiol 314(4), R623-R628 (2018).
Haddock CJ, Almeida-Pereira G, Stein LM, Yosten GLC, Samson WK. A novel regulator of thirst behavior: phoenixin. Am J Physiol Regul Integr Comp Physiol 318(6), R1027-R1035 (2020).
Yañez-Guerra LA, Thiel D, Jékely G. Pre-metazoan origin of neuropeptide signalling. Mol. Biol. Evol. doi: 10. 1093/molbev/msac051 (2022).
Herrington W, Lacey B, Sherliker P, Armitage J, Lewington S. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ. Res. 118(4), 535-546 (2016).
Lu J, Mitra S, Wang X, Khaidakov M, Mehta JL. Oxidative stress and lectin-like ox-LDL-receptor LOX-1 in atherogenesis and tumorigenesis. Antioxid. Redox Signal 15(8), 2301-2333 (2011).
Celik F, Aydin S. Blood and aqueous humor phoenixin, endocan and spexin in patients with diabetes mellitus and cataract with and without diabetic retinopathy. Peptides 150, 170728 (2022).