Generic placeholder image

Current Drug Targets

Author(s): Caroline Maria Oliveira Volpe, Tatiana Vaz, Fabiana Rocha-Silva, Pedro Henrique Villar-Delfino and José Augusto Nogueira-Machado*

DOI: 10.2174/1389450121666200225112055

DownloadDownload PDF Flyer Cite As
Is Galanin a Promising Therapeutic Resource for Neural and Nonneural Diseases?

Page: [922 - 929] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Background: Galanin (GAL) constitutes a family of neuropeptides composed of four peptides: (i) galanin (GAL), (ii) galanin-message associated peptide (GAMP), (iii) galanin-like peptide (GALP), and (iv) alarin. GAL contains 29/30 amino acids, and its biological action occurs through the interactions with its various receptors (GALR1, GALR2, and GALR3). The neuropeptide GAL regulates several physiological and pathophysiological functions in the central nervous system, the peripheral nervous system, and the peripheral organs. GAL is secreted mainly by oligodendrocytes, astrocytes, and the gastrointestinal tract, and its effect depends on the interaction with its different receptors. These receptors are expressed mainly in the central, peripheral nervous systems and the intestines.

Objective: The present review evaluates the role of GAL family in inflammatory diseases. An overview is given of the signaling and pharmacological effects due to the interaction between GAL and GALR in different cell types. The potential use of GAL as a therapeutic resource is critically discussed.

Conclusion: GAL is suggested to have an anti-inflammatory function in some situations and a proinflammatory function in others. The literature on GAL is controversial and currently not conclusive. This could be due to the complexity of the metabolic network signaling induced by the interactions between GAL and GALR. In the next future, GAL might be a promising therapeutic resource for several diseases, but its practical use for disease control is presently not advisable.

Keywords: Galanin, signaling, patents, neuropeptides, pro-inflammatory, anti-inflammatory.

Graphical Abstract

[1]
Lang R, Gundlach AL, Holmes FE, et al. Physiology, signaling, and pharmacology of galanin peptides and receptors: three decades of emerging diversity. Pharmacol Rev 2015; 67(1): 118-75.
[http://dx.doi.org/10.1124/pr.112.006536] [PMID: 25428932]
[2]
Tatemoto K, Rökaeus A, Jörnvall H, McDonald TJ, Mutt V. Galanin - a novel biologically active peptide from porcine intestine. FEBS Lett 1983; 164(1): 124-8.
[http://dx.doi.org/10.1016/0014-5793(83)80033-7] [PMID: 6197320]
[3]
Lyubetska H, Zhang L, Kong J, Vrontakis M. An elevated level of circulating galanin promotes developmental expression of myelin basic protein in the mouse brain. Neuroscience 2015; 284: 581-9.
[http://dx.doi.org/10.1016/j.neuroscience.2014.10.031] [PMID: 25450959]
[4]
Wraith DC, Pope R, Butzkueven H, et al. A role for galanin in human and experimental inflammatory demyelination. Proc Natl Acad Sci USA 2009; 106(36): 15466-71.
[http://dx.doi.org/10.1073/pnas.0903360106] [PMID: 19717462]
[5]
Kofler B, Evans HF, Liu ML, et al. Characterization of the 5′-flanking region of the human preprogalanin gene. DNA Cell Biol 1995; 14(4): 321-9.
[http://dx.doi.org/10.1089/dna.1995.14.321] [PMID: 7536007]
[6]
Kofler B, Lapsys N, Furler SM, Klaus C, Shine J, Iismaa TP. A polymorphism in the 3′ region of the human preprogalanin gene. Mol Cell Probes 1998; 12(6): 431-2.
[http://dx.doi.org/10.1006/mcpr.1998.0200] [PMID: 9843662]
[7]
Rökaeus A, Brownstein MJ. Construction of a porcine adrenal medullary cDNA library and nucleotide sequence analysis of two clones encoding a galanin precursor. Proc Natl Acad Sci USA 1986; 83(17): 6287-91.
[http://dx.doi.org/10.1073/pnas.83.17.6287] [PMID: 2428032]
[8]
Fang P, Shi M, Zhu Y, Bo P, Zhang Z. Type 2 diabetes mellitus as a disorder of galanin resistance. Exp Gerontol 2016; 73: 72-7.
[http://dx.doi.org/10.1016/j.exger.2015.11.007] [PMID: 26585047]
[9]
Kofler B, Berger A, Santic R, et al. Expression of neuropeptide galanin and galanin receptors in human skin. J Invest Dermatol 2004; 122(4): 1050-3.
[http://dx.doi.org/10.1111/j.0022-202X.2004.22418.x] [PMID: 15102097]
[10]
Lang R, Kofler B. The galanin peptide family in inflammation. Neuropeptides 2011; 45(1): 1-8.
[http://dx.doi.org/10.1016/j.npep.2010.10.005] [PMID: 21087790]
[11]
Bauer JW, Lang R, Jakab M, Kofler B. Galanin family of peptides in skin function. Cell Mol Life Sci 2008; 65(12): 1820-5.
[http://dx.doi.org/10.1007/s00018-008-8156-5] [PMID: 18500644]
[12]
Gudjonsson JE, Ding J, Li X, et al. Global gene expression analysis reveals evidence for decreased lipid biosynthesis and increased innate immunity in uninvolved psoriatic skin. J Invest Dermatol 2009; 129(12): 2795-804.
[http://dx.doi.org/10.1038/jid.2009.173] [PMID: 19571819]
[13]
Lang R, Gundlach AL, Kofler B. The galanin peptide family: receptor pharmacology, pleiotropic biological actions, and implications in health and disease. Pharmacol Ther 2007; 115(2): 177-207.
[http://dx.doi.org/10.1016/j.pharmthera.2007.05.009] [PMID: 17604107]
[14]
Locker F, Lang AA, Koller A, Lang R, Bianchini R, Kofler B. Galanin modulates human and murine neutrophil activation in vitro. Acta Physiol (Oxf) 2015; 213(3): 595-602.
[http://dx.doi.org/10.1111/apha.12444] [PMID: 25545502]
[15]
Bacon A, Holmes FE, Small CJ, et al. Transgenic over-expression of galanin in injured primary sensory neurons. Neuroreport 2002; 13(16): 2129-32.
[http://dx.doi.org/10.1097/00001756-200211150-00028] [PMID: 12438940]
[16]
McDonald AC, Schuijers JA, Shen PJ, Gundlach AL, Grills BL. Expression of galanin and galanin receptor-1 in normal bone and during fracture repair in the rat. Bone 2003; 33(5): 788-97.
[http://dx.doi.org/10.1016/S8756-3282(03)00244-8] [PMID: 14623054]
[17]
Bauer FE, Zintel A, Kenny MJ, Calder D, Ghatei MA, Bloom SR. Inhibitory effect of galanin on postprandial gastrointestinal motility and gut hormone release in humans. Gastroenterology 1989; 97(2): 260-4.
[http://dx.doi.org/10.1016/0016-5085(89)90059-0] [PMID: 2472997]
[18]
Bauer JW, Lang R, Jakab M, Kofler B. Galanin family of peptides in skin function. Exp Suppl 2010; 102: 51-9.
[http://dx.doi.org/10.1007/978-3-0346-0228-0_5] [PMID: 21299061]
[19]
Bishop AE, Polak JM, Bauer FE, Christofides ND, Carlei F, Bloom SR. Occurrence and distribution of a newly discovered peptide, galanin, in the mammalian enteric nervous system. Gut 1986; 27(7): 849-57.
[http://dx.doi.org/10.1136/gut.27.7.849] [PMID: 2426161]
[20]
Cheung A, Polak JM, Bauer FE, et al. Distribution of galanin immunoreactivity in the respiratory tract of pig, guinea pig, rat, and dog. Thorax 1985; 40(12): 889-96.
[http://dx.doi.org/10.1136/thx.40.12.889] [PMID: 2420020]
[21]
Ekblad E, Håkanson R, Sundler F, Wahlestedt C. Galanin: neuromodulatory and direct contractile effects on smooth muscle preparations. Br J Pharmacol 1985; 86(1): 241-6.
[http://dx.doi.org/10.1111/j.1476-5381.1985.tb09455.x] [PMID: 2413937]
[22]
Hulting AL, Meister B, Grimelius L, Wersäll J, Anggård A, Hökfelt T. Production of a galanin-like peptide by a human pituitary adenoma: immunohistochemical evidence. Acta Physiol Scand 1989; 137(4): 561-2.
[http://dx.doi.org/10.1111/j.1748-1716.1989.tb08801.x] [PMID: 2481382]
[23]
Jacobowitz DM, Kresse A, Skofitsch G. Galanin in the brain: chemoarchitectonics and brain cartography--a historical review. Peptides 2004; 25(3): 433-64.
[http://dx.doi.org/10.1016/j.peptides.2004.02.015] [PMID: 15134866]
[24]
Melander T, Staines WA. A galanin-like peptide coexists in putative cholinergic somata of the septum-basal forebrain complex and in acetylcholinesterase-containing fibers and varicosities within the hippocampus in the owl monkey (Aotus trivirgatus). Neurosci Lett 1986; 68(1): 17-22.
[http://dx.doi.org/10.1016/0304-3940(86)90222-3] [PMID: 2425307]
[25]
Melander T, Staines WA, Hökfelt T, et al. Galanin-like immunoreactivity in cholinergic neurons of the septum-basal forebrain complex projecting to the hippocampus of the rat. Brain Res 1985; 360(1-2): 130-8.
[http://dx.doi.org/10.1016/0006-8993(85)91228-4] [PMID: 2416401]
[26]
Melander T, Staines WA, Rökaeus A. Galanin-like immunoreactivity in hippocampal afferents in the rat, with special reference to cholinergic and noradrenergic inputs. Neuroscience 1986; 19(1): 223-40.
[http://dx.doi.org/10.1016/0306-4522(86)90017-5] [PMID: 2431348]
[27]
Branchek TA, Smith KE, Gerald C, Walker MW. Galanin receptor subtypes. Trends Pharmacol Sci 2000; 21(3): 109-17.
[http://dx.doi.org/10.1016/S0165-6147(00)01446-2] [PMID: 10689365]
[28]
Evans HF, Shine J. Human galanin: molecular cloning reveals a unique structure. Endocrinology 1991; 129(3): 1682-4.
[http://dx.doi.org/10.1210/endo-129-3-1682] [PMID: 1714839]
[29]
Kageyama H, Takenoya F, Kita T, Hori T, Guan JL, Shioda S. Galanin-like peptide in the brain: effects on feeding, energy metabolism and reproduction. Regul Pept 2005; 126(1-2): 21-6.
[http://dx.doi.org/10.1016/j.regpep.2004.08.029] [PMID: 15620409]
[30]
Santic R, Fenninger K, Graf K, et al. Gangliocytes in neuroblastic tumors express alarin, a novel peptide derived by differential splicing of the galanin-like peptide gene. J Mol Neurosci 2006; 29(2): 145-52.
[http://dx.doi.org/10.1385/JMN:29:2:145] [PMID: 16954604]
[31]
Webling KE, Runesson J, Bartfai T, Langel U. Galanin receptors and ligands. Front Endocrinol (Lausanne) 2012; 3: 146.
[http://dx.doi.org/10.3389/fendo.2012.00146] [PMID: 23233848]
[32]
Liu Z, Xu Y, Wu L, Zhang S. Evolution of galanin receptor genes: insights from the deuterostome genomes. J Biomol Struct Dyn 2010; 28(1): 97-106.
[http://dx.doi.org/10.1080/07391102.2010.10507346] [PMID: 20476798]
[33]
Wang S, Hashemi T, He C, Strader C, Bayne M. Molecular cloning and pharmacological characterization of a new galanin receptor subtype. Mol Pharmacol 1997; 52(3): 337-43.
[http://dx.doi.org/10.1124/mol.52.3.337] [PMID: 9281594]
[34]
Wang S, He C, Hashemi T, Bayne M. Cloning and expressional characterization of a novel galanin receptor. Identification of different pharmacophores within galanin for the three galanin receptor subtypes. J Biol Chem 1997; 272(51): 31949-52.
[http://dx.doi.org/10.1074/jbc.272.51.31949] [PMID: 9405385]
[35]
Habert-Ortoli E, Amiranoff B, Loquet I, Laburthe M, Mayaux JF. Molecular cloning of a functional human galanin receptor. Proc Natl Acad Sci USA 1994; 91(21): 9780-3.
[http://dx.doi.org/10.1073/pnas.91.21.9780] [PMID: 7524088]
[36]
Lorimer DD, Benya RV. Cloning and quantification of galanin-1 receptor expression by mucosal cells lining the human gastrointestinal tract. Biochem Biophys Res Commun 1996; 222(2): 379-85.
[http://dx.doi.org/10.1006/bbrc.1996.0752] [PMID: 8670213]
[37]
Smith KE, Forray C, Walker MW, et al. Expression cloning of a rat hypothalamic galanin receptor coupled to phosphoinositide turnover. J Biol Chem 1997; 272(39): 24612-6.
[http://dx.doi.org/10.1074/jbc.272.39.24612] [PMID: 9305929]
[38]
Bloomquist BT, Beauchamp MR, Zhelnin L, et al. Cloning and expression of the human galanin receptor GalR2. Biochem Biophys Res Commun 1998; 243(2): 474-9.
[http://dx.doi.org/10.1006/bbrc.1998.8133] [PMID: 9480833]
[39]
Fathi Z, Battaglino PM, Iben LG, et al. Molecular characterization, pharmacological properties and chromosomal localization of the human GALR2 galanin receptor. Brain Res Mol Brain Res 1998; 58(1-2): 156-69.
[http://dx.doi.org/10.1016/S0169-328X(98)00116-8] [PMID: 9685625]
[40]
Fathi Z, Cunningham AM, Iben LG, et al. Cloning, pharmacological characterization and distribution of a novel galanin receptor. Brain Res Mol Brain Res 1997; 51(1-2): 49-59.
[http://dx.doi.org/10.1016/S0169-328X(97)00210-6] [PMID: 9427506]
[41]
Smith KE, Walker MW, Artymyshyn R, et al. Cloned human and rat galanin GALR3 receptors. Pharmacology and activation of G-protein inwardly rectifying K+ channels. J Biol Chem 1998; 273(36): 23321-6.
[http://dx.doi.org/10.1074/jbc.273.36.23321] [PMID: 9722565]
[42]
Kolakowski LF Jr, O’Neill GP, Howard AD, et al. Molecular characterization and expression of cloned human galanin receptors GALR2 and GALR3. J Neurochem 1998; 71(6): 2239-51.
[http://dx.doi.org/10.1046/j.1471-4159.1998.71062239.x] [PMID: 9832121]
[43]
Kanazawa T, Iwashita T, Kommareddi P, et al. Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors. Oncogene 2007; 26(39): 5762-71.
[http://dx.doi.org/10.1038/sj.onc.1210384] [PMID: 17384686]
[44]
Florén A, Land T, Langel U. Galanin receptor subtypes and ligand binding. Neuropeptides 2000; 34(6): 331-7.
[http://dx.doi.org/10.1054/npep.2000.0808] [PMID: 11162289]
[45]
Wang S, He C, Maguire MT, et al. Genomic organization and functional characterization of the mouse GalR1 galanin receptor. FEBS Lett 1997; 411(2-3): 225-30.
[http://dx.doi.org/10.1016/S0014-5793(97)00695-9] [PMID: 9271210]
[46]
Šípková J, Kramáriková I, Hynie S, Klenerová V. The galanin and galanin receptor subtypes, its regulatory role in the biological and pathological functions. Physiol Res 2017; 66(5): 729-40.
[http://dx.doi.org/10.33549/physiolres.933576] [PMID: 28730831]
[47]
Botz B, Kemény Á, Brunner SM, et al. Lack of Galanin 3 Receptor Aggravates Murine Autoimmune Arthritis. J Mol Neurosci 2016; 59(2): 260-9.
[http://dx.doi.org/10.1007/s12031-016-0732-9] [PMID: 26941032]
[48]
Kofler B, Brunner S, Koller A, et al. Contribution of the galanin system to inflammation. Springerplus 2015; 4(Suppl. 1): L57.
[http://dx.doi.org/10.1186/2193-1801-4-S1-L57] [PMID: 27386220]
[49]
Stokoe D, Stephens LR, Copeland T, et al. Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 1997; 277(5325): 567-70.
[http://dx.doi.org/10.1126/science.277.5325.567] [PMID: 9228007]
[50]
Alessi DR, James SR, Downes CP, et al. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. Curr Biol 1997; 7(4): 261-9.
[http://dx.doi.org/10.1016/S0960-9822(06)00122-9] [PMID: 9094314]
[51]
Krasnow SM, Hohmann JG, Gragerov A, Clifton DK, Steiner RA. Analysis of the contribution of galanin receptors 1 and 2 to the central actions of galanin-like peptide. Neuroendocrinology 2004; 79(5): 268-77.
[http://dx.doi.org/10.1159/000079632] [PMID: 15249737]
[52]
Corness JD, Burbach JP, Hökfelt T. The rat galanin-gene promoter: response to members of the nuclear hormone receptor family, phorbol ester and forskolin. Brain Res Mol Brain Res 1997; 47(1-2): 11-23.
[http://dx.doi.org/10.1016/S0169-328X(97)00004-1] [PMID: 9221897]
[53]
Rökaeus A, Pruss RM, Eiden LE. Galanin gene expression in chromaffin cells is controlled by calcium and protein kinase signaling pathways. Endocrinology 1990; 127(6): 3096-102.
[http://dx.doi.org/10.1210/endo-127-6-3096] [PMID: 1701135]
[54]
Celi F, Bini V, Papi F, et al. Circulating acylated and total ghrelin and galanin in children with insulin-treated type 1 diabetes: relationship to insulin therapy, metabolic control and pubertal development. Clin Endocrinol (Oxf) 2005; 63(2): 139-45.
[http://dx.doi.org/10.1111/j.1365-2265.2005.02313.x] [PMID: 16060906]
[55]
Fang P, Bo P, Shi M, Yu M, Zhang Z. Circulating galanin levels are increased in patients with gestational diabetes mellitus. Clin Biochem 2013; 46(9): 831-3.
[http://dx.doi.org/10.1016/j.clinbiochem.2012.12.013] [PMID: 23266294]
[56]
Legakis I, Mantzouridis T, Mountokalakis T. Positive correlation of galanin with glucose in type 2 diabetes. Diabetes Care 2005; 28(3): 759-60.
[http://dx.doi.org/10.2337/diacare.28.3.759] [PMID: 15735230]
[57]
Rauch I, Kofler B. The galanin system in cancer. Exp Suppl 2010; 102: 223-41.
[PMID: 21299072]
[58]
Nagayoshi K, Ueki T, Tashiro K, et al. Galanin plays an important role in cancer invasiveness and is associated with poor prognosis in stage II colorectal cancer. Oncol Rep 2015; 33(2): 539-46.
[http://dx.doi.org/10.3892/or.2014.3660] [PMID: 25504183]
[59]
Zhang Z, Gu C, Fang P, et al. Endogenous galanin as a novel biomarker to predict gestational diabetes mellitus. Peptides 2014; 54: 186-9.
[http://dx.doi.org/10.1016/j.peptides.2014.01.024] [PMID: 24503374]
[60]
Banerjee R, Van Tubergen EA, Scanlon CS, et al. The G protein-coupled receptor GALR2 promotes angiogenesis in head and neck cancer. Mol Cancer Ther 2014; 13(5): 1323-33.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0904] [PMID: 24568968]
[61]
Timotin A, Pisarenko O, Sidorova M, et al. Myocardial protection from ischemia/reperfusion injury by exogenous galanin fragment. Oncotarget 2017; 8(13): 21241-52.
[http://dx.doi.org/10.18632/oncotarget.15071] [PMID: 28177906]
[62]
Pham T, Guerrini S, Wong H, Reeve J Jr, Sternini C. Distribution of galanin receptor 1 immunoreactivity in the rat stomach and small intestine. J Comp Neurol 2002; 450(3): 292-302.
[http://dx.doi.org/10.1002/cne.10311] [PMID: 12209857]
[63]
Locker F, Vidali S, Holub BS, et al. Lack of Galanin Receptor 3 Alleviates Psoriasis by Altering Vascularization, Immune Cell Infiltration, and Cytokine Expression. J Invest Dermatol 2018; 138(1): 199-207.
[http://dx.doi.org/10.1016/j.jid.2017.08.015] [PMID: 28844939]
[64]
Koller A, Bianchini R, Schlager S, Münz C, Kofler B, Wiesmayr S. The neuropeptide galanin modulates natural killer cell function. Neuropeptides 2017; 64: 109-15.
[http://dx.doi.org/10.1016/j.npep.2016.11.002] [PMID: 27837916]
[65]
Ramspacher A, Neudert M, Koller A, Schlager S, Kofler B, Brunner SM. Influence of the regulatory peptide galanin on cytokine expression in human monocytes. Ann N Y Acad Sci 2019; 1455(1): 185-95.
[http://dx.doi.org/10.1111/nyas.14111] [PMID: 31074091]
[66]
Dallos A, Kiss M, Polyánka H, Dobozy A, Kemény L, Husz S. Galanin receptor expression in cultured human keratinocytes and in normal human skin. J Peripher Nerv Syst 2006; 11(2): 156-64.
[http://dx.doi.org/10.1111/j.1085-9489.2006.00081.x] [PMID: 16787514]
[67]
Holub BS, Rauch I, Radner S, Sperl W, Hell M, Kofler B. Effects of galanin message-associated peptide and neuropeptide Y against various non-albicans Candida strains. Int J Antimicrob Agents 2011; 38(1): 76-80.
[http://dx.doi.org/10.1016/j.ijantimicag.2011.02.019] [PMID: 21550784]
[68]
Metz M, Maurer M. Innate immunity and allergy in the skin. Curr Opin Immunol 2009; 21(6): 687-93.
[http://dx.doi.org/10.1016/j.coi.2009.09.009] [PMID: 19828302]
[69]
Rauch I, Lundström L, Hell M, Sperl W, Kofler B. Galanin message-associated peptide suppresses growth and the budded-to-hyphal-form transition of Candida albicans. Antimicrob Agents Chemother 2007; 51(11): 4167-70.
[http://dx.doi.org/10.1128/AAC.00166-07] [PMID: 17698619]
[70]
Wada A, Wong PF, Hojo H, et al. Alarin but not its alternative-splicing form, GALP (Galanin-like peptide) has antimicrobial activity. Biochem Biophys Res Commun 2013; 434(2): 223-7.
[http://dx.doi.org/10.1016/j.bbrc.2013.03.045] [PMID: 23537644]
[71]
Su Y, Ganea D, Peng X, Jonakait GM. Galanin down-regulates microglial tumor necrosis factor-alpha production by a post-transcriptional mechanism. J Neuroimmunol 2003; 134(1-2): 52-60.
[http://dx.doi.org/10.1016/S0165-5728(02)00397-1] [PMID: 12507772]
[72]
Lee MJ, Oh JH, Park CH, Kim KH, Lee DH, Chung JH. Galanin contributes to ultraviolet irradiation-induced inflammation in human skin. Exp Dermatol 2017; 26(8): 744-7.
[http://dx.doi.org/10.1111/exd.13268] [PMID: 27943416]
[73]
Song J, Kim OY. Galanin’s implications for post-stroke improvement. Anat Cell Biol 2016; 49(4): 223-30.
[http://dx.doi.org/10.5115/acb.2016.49.4.223] [PMID: 28127496]
[74]
McMillin M, Frampton G, Grant S, DeMorrow S. The Neuropeptide Galanin Is Up-Regulated during Cholestasis and Contributes to Cholangiocyte Proliferation. Am J Pathol 2017; 187(4): 819-30.
[http://dx.doi.org/10.1016/j.ajpath.2016.12.015] [PMID: 28196718]
[75]
https://patents.google.com/?q=galanin2019
[76]
Smith KE, Gerald CPG, Weinshank RL, Linemeyer DL, Branchek TA, Forray C. Method of identifying ligands which bind recombinant galanin receptor (GALR2). Patent US5972624A 1996 October 26;
[77]
Aaron W, Austin RJ, Hart CL, Hoey TC, Kassner PD, Piper DE, et al. Anti-galanin antibodies and uses thereof. Patent US7371381B2 2003; May 13;
[78]
Crhisten U. Combination therapy for the treatment of autoimmune diseases. Patent US20170021018A1 2017 January 26;
[79]
Mjalli AMM, Gaddam B, Rao M, Bondlela M, Gopalaswamy R, Andrews RC, et al. Bissulfonamide compounds as agonists of GalR1, compositions, and methods of use. Patent US7582673B2 2009 September 1
[80]
Andrews RC, Hari A. Bis-sulfonamide derivatives, compositions, and methods of use. Patent WO2011022207A1 2011 February 24
[81]
Juhasz G, Hullam G, Eszlari N, et al. Brain galanin system genes interact with life stresses in depression-related phenotypes. Proc Natl Acad Sci USA 2014; 111(16): E1666-73.
[http://dx.doi.org/10.1073/pnas.1403649111] [PMID: 24706871]
[82]
Barde S, Rüegg J, Prud’homme J, Ekström TJ, Palkovits M, et al. Alterations in the neuropeptide galanin system in major depressive disorder involve levels of transcripts, methylation, and peptide. Proceedings of the National Academy of Sciences.
[http://dx.doi.org/10.1073/pnas.1617824113]