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
[http://dx.doi.org/10.1124/pr.112.006536] [PMID: 25428932]
[http://dx.doi.org/10.1016/0014-5793(83)80033-7] [PMID: 6197320]
[http://dx.doi.org/10.1016/j.neuroscience.2014.10.031] [PMID: 25450959]
[http://dx.doi.org/10.1073/pnas.0903360106] [PMID: 19717462]
[http://dx.doi.org/10.1089/dna.1995.14.321] [PMID: 7536007]
[http://dx.doi.org/10.1006/mcpr.1998.0200] [PMID: 9843662]
[http://dx.doi.org/10.1073/pnas.83.17.6287] [PMID: 2428032]
[http://dx.doi.org/10.1016/j.exger.2015.11.007] [PMID: 26585047]
[http://dx.doi.org/10.1111/j.0022-202X.2004.22418.x] [PMID: 15102097]
[http://dx.doi.org/10.1016/j.npep.2010.10.005] [PMID: 21087790]
[http://dx.doi.org/10.1007/s00018-008-8156-5] [PMID: 18500644]
[http://dx.doi.org/10.1038/jid.2009.173] [PMID: 19571819]
[http://dx.doi.org/10.1016/j.pharmthera.2007.05.009] [PMID: 17604107]
[http://dx.doi.org/10.1111/apha.12444] [PMID: 25545502]
[http://dx.doi.org/10.1097/00001756-200211150-00028] [PMID: 12438940]
[http://dx.doi.org/10.1016/S8756-3282(03)00244-8] [PMID: 14623054]
[http://dx.doi.org/10.1016/0016-5085(89)90059-0] [PMID: 2472997]
[http://dx.doi.org/10.1007/978-3-0346-0228-0_5] [PMID: 21299061]
[http://dx.doi.org/10.1136/gut.27.7.849] [PMID: 2426161]
[http://dx.doi.org/10.1136/thx.40.12.889] [PMID: 2420020]
[http://dx.doi.org/10.1111/j.1476-5381.1985.tb09455.x] [PMID: 2413937]
[http://dx.doi.org/10.1111/j.1748-1716.1989.tb08801.x] [PMID: 2481382]
[http://dx.doi.org/10.1016/j.peptides.2004.02.015] [PMID: 15134866]
[http://dx.doi.org/10.1016/0304-3940(86)90222-3] [PMID: 2425307]
[http://dx.doi.org/10.1016/0006-8993(85)91228-4] [PMID: 2416401]
[http://dx.doi.org/10.1016/0306-4522(86)90017-5] [PMID: 2431348]
[http://dx.doi.org/10.1016/S0165-6147(00)01446-2] [PMID: 10689365]
[http://dx.doi.org/10.1210/endo-129-3-1682] [PMID: 1714839]
[http://dx.doi.org/10.1016/j.regpep.2004.08.029] [PMID: 15620409]
[http://dx.doi.org/10.1385/JMN:29:2:145] [PMID: 16954604]
[http://dx.doi.org/10.3389/fendo.2012.00146] [PMID: 23233848]
[http://dx.doi.org/10.1080/07391102.2010.10507346] [PMID: 20476798]
[http://dx.doi.org/10.1124/mol.52.3.337] [PMID: 9281594]
[http://dx.doi.org/10.1074/jbc.272.51.31949] [PMID: 9405385]
[http://dx.doi.org/10.1073/pnas.91.21.9780] [PMID: 7524088]
[http://dx.doi.org/10.1006/bbrc.1996.0752] [PMID: 8670213]
[http://dx.doi.org/10.1074/jbc.272.39.24612] [PMID: 9305929]
[http://dx.doi.org/10.1006/bbrc.1998.8133] [PMID: 9480833]
[http://dx.doi.org/10.1016/S0169-328X(98)00116-8] [PMID: 9685625]
[http://dx.doi.org/10.1016/S0169-328X(97)00210-6] [PMID: 9427506]
[http://dx.doi.org/10.1074/jbc.273.36.23321] [PMID: 9722565]
[http://dx.doi.org/10.1046/j.1471-4159.1998.71062239.x] [PMID: 9832121]
[http://dx.doi.org/10.1038/sj.onc.1210384] [PMID: 17384686]
[http://dx.doi.org/10.1054/npep.2000.0808] [PMID: 11162289]
[http://dx.doi.org/10.1016/S0014-5793(97)00695-9] [PMID: 9271210]
[http://dx.doi.org/10.33549/physiolres.933576] [PMID: 28730831]
[http://dx.doi.org/10.1007/s12031-016-0732-9] [PMID: 26941032]
[http://dx.doi.org/10.1186/2193-1801-4-S1-L57] [PMID: 27386220]
[http://dx.doi.org/10.1126/science.277.5325.567] [PMID: 9228007]
[http://dx.doi.org/10.1016/S0960-9822(06)00122-9] [PMID: 9094314]
[http://dx.doi.org/10.1159/000079632] [PMID: 15249737]
[http://dx.doi.org/10.1016/S0169-328X(97)00004-1] [PMID: 9221897]
[http://dx.doi.org/10.1210/endo-127-6-3096] [PMID: 1701135]
[http://dx.doi.org/10.1111/j.1365-2265.2005.02313.x] [PMID: 16060906]
[http://dx.doi.org/10.1016/j.clinbiochem.2012.12.013] [PMID: 23266294]
[http://dx.doi.org/10.2337/diacare.28.3.759] [PMID: 15735230]
[http://dx.doi.org/10.3892/or.2014.3660] [PMID: 25504183]
[http://dx.doi.org/10.1016/j.peptides.2014.01.024] [PMID: 24503374]
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0904] [PMID: 24568968]
[http://dx.doi.org/10.18632/oncotarget.15071] [PMID: 28177906]
[http://dx.doi.org/10.1002/cne.10311] [PMID: 12209857]
[http://dx.doi.org/10.1016/j.jid.2017.08.015] [PMID: 28844939]
[http://dx.doi.org/10.1016/j.npep.2016.11.002] [PMID: 27837916]
[http://dx.doi.org/10.1111/nyas.14111] [PMID: 31074091]
[http://dx.doi.org/10.1111/j.1085-9489.2006.00081.x] [PMID: 16787514]
[http://dx.doi.org/10.1016/j.ijantimicag.2011.02.019] [PMID: 21550784]
[http://dx.doi.org/10.1016/j.coi.2009.09.009] [PMID: 19828302]
[http://dx.doi.org/10.1128/AAC.00166-07] [PMID: 17698619]
[http://dx.doi.org/10.1016/j.bbrc.2013.03.045] [PMID: 23537644]
[http://dx.doi.org/10.1016/S0165-5728(02)00397-1] [PMID: 12507772]
[http://dx.doi.org/10.1111/exd.13268] [PMID: 27943416]
[http://dx.doi.org/10.5115/acb.2016.49.4.223] [PMID: 28127496]
[http://dx.doi.org/10.1016/j.ajpath.2016.12.015] [PMID: 28196718]
[http://dx.doi.org/10.1073/pnas.1403649111] [PMID: 24706871]
[http://dx.doi.org/10.1073/pnas.1617824113]