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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Review Article

Translocator Protein 18-kDa: A Promising Target to Treat Neuroinflammation- related Degenerative Diseases

Author(s): Chiara Tremolanti, Lorenzo Germelli, Elisabetta Barresi, Eleonora Da Pozzo*, Francesca Simorini, Sabrina Castellano, Sabrina Taliani*, Federico Da Settimo, Claudia Martini and Barbara Costa

Volume 29, Issue 28, 2022

Published on: 31 May, 2022

Page: [4831 - 4861] Pages: 31

DOI: 10.2174/0929867329666220415120820

Price: $65

Abstract

In the nervous system, inflammatory responses physiologically occur as defense mechanisms triggered by damaging events. If improperly regulated, neuroinflammation can contribute to the development of chronically activated states of glial cells, with the perpetuation of inflammation and neuronal damage, thus leading to neurological and neurodegenerative disorders. Interestingly, neuroinflammation is associated with the overexpression of the mitochondrial translocator protein (TSPO) in activated glia. Despite the precise role of TSPO in the immunomodulatory mechanisms during active disease states is still unclear, it has emerged as a promising target to promote neuroprotection. Indeed, TSPO ligands have been shown to exert beneficial effects in counteracting neuroinflammation and neuronal damage in several in vitro and in vivo models of neurodegenerative diseases. In particular, the regulation of neurosteroids’ production, cytokine release, metabolism of radical oxidative species, and cellular bioenergetics appear to be the main cellular events that underlie the observed effects. The present review aims to illustrate and summarize recent findings on the potential effect of TSPO ligands against neuroinflammation and related neurodegenerative mechanisms, taking into consideration some pathologies of the nervous system in which inflammatory events are crucial for the onset and progression of the disease and attempting to shed light onto the immunomodulatory effects of TSPO.

Keywords: Translocator protein 18kDa, TSPO, structure-activity relationship, selective ligands, neuroinflammation, microglia, astrocytes, neurons.

« Previous Next »
[1]
Papadopoulos, V.; Baraldi, M.; Guilarte, T.R.; Knudsen, T.B.; Lacapère, J.J.; Lindemann, P.; Norenberg, M.D.; Nutt, D.; Weizman, A.; Zhang, M.R.; Gavish, M. Translocator protein (18kDa): New nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol. Sci., 2006, 27(8), 402-409.
[http://dx.doi.org/10.1016/j.tips.2006.06.005] [PMID: 16822554]
[2]
Jaremko, L.; Jaremko, M.; Giller, K.; Becker, S.; Zweckstetter, M. Structure of the mitochondrial translocator protein in complex with a diagnostic ligand. Science, 2014, 343(6177), 1363-1366.
[http://dx.doi.org/10.1126/science.1248725] [PMID: 24653034]
[3]
Fan, J.; Papadopoulos, V. Evolutionary origin of the mitochondrial cholesterol transport machinery reveals a universal mechanism of steroid hormone biosynthesis in animals. PLoS One, 2013, 8(10), e76701.
[http://dx.doi.org/10.1371/journal.pone.0076701] [PMID: 24124589]
[4]
Lacapère, J.J.; Papadopoulos, V. Peripheral-type benzodiazepine receptor: Structure and function of a cholesterol-binding protein in steroid and bile acid biosynthesis. Steroids, 2003, 68(7-8), 569-585.
[http://dx.doi.org/10.1016/S0039-128X(03)00101-6] [PMID: 12957662]
[5]
Li, H.; Papadopoulos, V. Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern. Endocrinology, 1998, 139(12), 4991-4997.
[http://dx.doi.org/10.1210/endo.139.12.6390] [PMID: 9832438]
[6]
Owen, D.R.; Yeo, A.J.; Gunn, R.N.; Song, K.; Wadsworth, G.; Lewis, A.; Rhodes, C.; Pulford, D.J.; Bennacef, I.; Parker, C.A.; StJean, P.L.; Cardon, L.R.; Mooser, V.E.; Matthews, P.M.; Rabiner, E.A.; Rubio, J.P. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J. Cereb. Blood Flow Metab., 2012, 32(1), 1-5.
[http://dx.doi.org/10.1038/jcbfm.2011.147] [PMID: 22008728]
[7]
Costa, B.; Pini, S.; Gabelloni, P.; Da Pozzo, E.; Abelli, M.; Lari, L.; Preve, M.; Lucacchini, A.; Cassano, G.B.; Martini, C. The spontaneous Ala147Thr amino acid substitution within the translocator protein influences pregnenolone production in lymphomonocytes of healthy individuals. Endocrinology, 2009, 150(12), 5438-5445.
[http://dx.doi.org/10.1210/en.2009-0752] [PMID: 19846611]
[8]
Fantini, J.; Di Scala, C.; Baier, C.J.; Barrantes, F.J. Molecular mechanisms of protein-cholesterol interactions in plasma membranes: Functional distinction between topological (tilted) and consensus (CARC/CRAC) domains. Chem. Phys. Lipids, 2016, 199, 52-60.
[http://dx.doi.org/10.1016/j.chemphyslip.2016.02.009] [PMID: 26987951]
[9]
Costa, B.; Da Pozzo, E.; Martini, C. 18-kDa translocator protein association complexes in the brain: From structure to function. Biochem. Pharmacol., 2020, 177, 114015.
[http://dx.doi.org/10.1016/j.bcp.2020.114015] [PMID: 32387458]
[10]
Li, F.; Liu, J.; Zheng, Y.; Garavito, R.M.; Ferguson-Miller, S. Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism. Science, 2015, 347(6221), 555-558.
[http://dx.doi.org/10.1126/science.1260590]
[11]
Guo, Y.; Kalathur, R.C.; Liu, Q.; Kloss, B.; Bruni, R.; Ginter, C.; Kloppmann, E.; Rost, B.; Hendrickson, W.A. Structure and activity of tryptophan-rich TSPO proteins. Science, 2015, 347(6221), 551-555.
[http://dx.doi.org/10.1126/science.aaa1534]
[12]
Notter, T.; Schalbetter, S.M.; Clifton, N.E.; Mattei, D.; Richetto, J.; Thomas, K.; Meyer, U.; Hall, J. Neuronal activity increases translocator protein (TSPO) levels. Mol. Psychiatry, 2021, 26, 2025-2037.
[http://dx.doi.org/10.1038/s41380-020-0745-1] [PMID: 32398717]
[13]
Batarseh, A.; Papadopoulos, V. Regulation of translocator protein 18 kDa (TSPO) expression in health and disease states. Mol. Cell. Endocrinol., 2010, 327(1-2), 1-12.
[http://dx.doi.org/10.1016/j.mce.2010.06.013] [PMID: 20600583]
[14]
Betlazar, C.; Harrison-Brown, M.; Middleton, R.J.; Banati, R.; Liu, G.J. Cellular sources and regional variations in the expression of the neuroinflammatory marker translocator protein (TSPO) in the normal brain. Int. J. Mol. Sci., 2018, 19(9), 2707.
[http://dx.doi.org/10.3390/ijms19092707] [PMID: 30208620]
[15]
Herrera-Rivero, M.; Heneka, M.T.; Papadopoulos, V. Translocator protein and new targets for neuroinflammation. Clin. Transl. Imaging, 2015, 3(6), 391-402.
[http://dx.doi.org/10.1007/s40336-015-0151-x]
[16]
Chen, M.K.; Guilarte, T.R. Translocator protein 18 kDa (TSPO): Molecular sensor of brain injury and repair. Pharmacol. Ther., 2008, 118(1), 1-17.
[http://dx.doi.org/10.1016/j.pharmthera.2007.12.004] [PMID: 18374421]
[17]
Bonsack, F.; Sukumari-Ramesh, S. TSPO: An evolutionarily conserved protein with elusive functions. Int. J. Mol. Sci., 2018, 19(6), 1694.
[http://dx.doi.org/10.3390/ijms19061694] [PMID: 29875327]
[18]
Veenman, L.; Shandalov, Y.; Gavish, M. VDAC activation by the 18 kDa translocator protein (TSPO), implications for apoptosis. J. Bioenerg. Biomembr., 2008, 40(3), 199-205.
[http://dx.doi.org/10.1007/s10863-008-9142-1] [PMID: 18670869]
[19]
Costa, B.; Da Pozzo, E.; Giacomelli, C.; Taliani, S.; Bendinelli, S.; Barresi, E.; Da Settimo, F.; Martini, C. TSPO ligand residence time influences human glioblastoma multiforme cell death/life balance. Apoptosis, 2015, 20(3), 383-398.
[http://dx.doi.org/10.1007/s10495-014-1063-3] [PMID: 25413799]
[20]
Elkamhawy, A.; Park, J.E.; Hassan, A.H.E.; Pae, A.N.; Lee, J.; Park, B.G.; Paik, S.; Do, J.; Park, J.H.; Park, K.D.; Moon, B.; Park, W.K.; Cho, H.; Jeong, D.Y.; Roh, E.J. Design, synthesis, biological evaluation and molecular modelling of 2-(2-aryloxyphenyl)-1,4-dihydroisoquinolin-3(2H)-ones: A novel class of TSPO ligands modulating amyloid-β-induced mPTP opening. Eur. J. Pharm. Sci., 2017, 104, 366-381.
[http://dx.doi.org/10.1016/j.ejps.2017.04.015] [PMID: 28435076]
[21]
Da Pozzo, E.; Giacomelli, C.; Costa, B.; Cavallini, C.; Taliani, S.; Barresi, E.; Da Settimo, F.; Martini, C. TSPO PIGA ligands promote neurosteroidogenesis and human astrocyte well-being. Int. J. Mol. Sci., 2016, 17(7), 1028.
[http://dx.doi.org/10.3390/ijms17071028] [PMID: 27367681]
[22]
Korneyev, A.; Pan, B.S.; Polo, A.; Romeo, E.; Guidotti, A.; Costa, E. Stimulation of brain pregnenolone synthesis by mitochondrial diazepam binding inhibitor receptor ligands in vivo. J. Neurochem., 1993, 61(4), 1515-1524.
[http://dx.doi.org/10.1111/j.1471-4159.1993.tb13647.x] [PMID: 8397297]
[23]
Verleye, M.; Akwa, Y.; Liere, P.; Ladurelle, N.; Pianos, A.; Eychenne, B.; Schumacher, M.; Gillardin, J.M. The anxiolytic etifoxine activates the peripheral benzodiazepine receptor and increases the neurosteroid levels in rat brain. Pharmacol. Biochem. Behav., 2005, 82(4), 712-720.
[http://dx.doi.org/10.1016/j.pbb.2005.11.013] [PMID: 16388839]
[24]
Bitran, D.; Foley, M.; Audette, D.; Leslie, N.; Frye, C.A. Activation of peripheral mitochondrial benzodiazepine receptors in the hippocampus stimulates allopregnanolone synthesis and produces anxiolytic-like effects in the rat. Psychopharmacology (Berl.), 2000, 151(1), 64-71.
[http://dx.doi.org/10.1007/s002130000471] [PMID: 10958118]
[25]
Wolf, L.; Bauer, A.; Melchner, D.; Hallof-Buestrich, H.; Stoertebecker, P.; Haen, E.; Kreutz, M.; Sarubin, N.; Milenkovic, V.M.; Wetzel, C.H.; Rupprecht, R.; Nothdurfter, C. Enhancing neurosteroid synthesis--relationship to the pharmacology of translocator protein (18 kDa) (TSPO) ligands and benzodiazepines. Pharmacopsychiatry, 2015, 48(2), 72-77.
[http://dx.doi.org/10.1055/s-0034-1398507] [PMID: 25654303]
[26]
Costa, B.; Da Pozzo, E.; Giacomelli, C.; Barresi, E.; Taliani, S.; Da Settimo, F.; Martini, C. TSPO ligand residence time: A new parameter to predict compound neurosteroidogenic efficacy. Sci. Rep., 2016, 6(1), 18164.
[http://dx.doi.org/10.1038/srep18164] [PMID: 26750656]
[27]
Costa, B.; Taliani, S.; Da Pozzo, E.; Barresi, E.; Robello, M.; Cavallini, C.; Cosconati, S.; Da Settimo, F.; Novellino, E.; Martini, C. Residence time, a new parameter to predict neurosteroidogenic efficacy of translocator protein (TSPO) ligands: The case study of N,N-Dialkyl-2-arylindol-3-ylglyoxylamides. ChemMedChem, 2017, 12(16), 1275-1278.
[http://dx.doi.org/10.1002/cmdc.201700220] [PMID: 28467680]
[28]
Costa, B.; Da Pozzo, E.; Martini, C. Translocator protein and steroidogenesis. Biochem. J., 2018, 475(5), 901-904.
[http://dx.doi.org/10.1042/BCJ20170766] [PMID: 29511094]
[29]
Selvaraj, V.; Tu, L.N.; Stocco, D.M. Crucial role reported for TSPO in viability and steroidogenesis is a misconception. Commentary: Conditional steroidogenic cell-targeted deletion of TSPO unveils a crucial role in viability and hormone-dependent steroid formation. Front. Endocrinol. (Lausanne), 2016, 7, 91.
[http://dx.doi.org/10.3389/fendo.2016.00091] [PMID: 27489176]
[30]
Fan, J.; Campioli, E.; Midzak, A.; Culty, M.; Papadopoulos, V. Conditional steroidogenic cell-targeted deletion of TSPO unveils a crucial role in viability and hormone-dependent steroid formation. Proc. Natl. Acad. Sci. USA, 2015, 112(23), 7261-7266.
[http://dx.doi.org/10.1073/pnas.1502670112] [PMID: 26039990]
[31]
Tu, L.N.; Morohaku, K.; Manna, P.R.; Pelton, S.H.; Butler, W.R.; Stocco, D.M.; Selvaraj, V. Peripheral benzodiazepine receptor/translocator protein global knock-out mice are viable with no effects on steroid hormone biosynthesis. J. Biol. Chem., 2014, 289(40), 27444-27454.
[http://dx.doi.org/10.1074/jbc.M114.578286] [PMID: 24936060]
[32]
Banati, R.B.; Middleton, R.J.; Chan, R.; Hatty, C.R.; Kam, W.W.; Quin, C.; Graeber, M.B.; Parmar, A.; Zahra, D.; Callaghan, P.; Fok, S.; Howell, N.R.; Gregoire, M.; Szabo, A.; Pham, T.; Davis, E.; Liu, G.J. Positron emission tomography and functional characterization of a complete PBR/TSPO knockout. Nat. Commun., 2014, 5(1), 5452.
[http://dx.doi.org/10.1038/ncomms6452] [PMID: 25406832]
[33]
Morohaku, K.; Pelton, S.H.; Daugherty, D.J.; Butler, W.R.; Deng, W.; Selvaraj, V. Translocator protein/peripheral benzodiazepine receptor is not required for steroid hormone biosynthesis. Endocrinology, 2014, 155(1), 89-97.
[http://dx.doi.org/10.1210/en.2013-1556] [PMID: 24174323]
[34]
Papadopoulos, V. Peripheral-type benzodiazepine/diazepam binding inhibitor receptor: Biological role in steroidogenic cell function. Endocr. Rev., 1993, 14(2), 222-240.
[http://dx.doi.org/10.1210/edrv-14-2-222] [PMID: 8391980]
[35]
Veenman, L.; Gavish, M. The peripheral-type benzodiazepine receptor and the cardiovascular system. Implications for drug development. Pharmacol. Ther., 2006, 110(3), 503-524.
[http://dx.doi.org/10.1016/j.pharmthera.2005.09.007] [PMID: 16337685]
[36]
Taliani, S.; Da Settimo, F.; Da Pozzo, E.; Chelli, B.; Martini, C. Translocator protein ligands as promising therapeutic tools for anxiety disorders. Curr. Med. Chem., 2009, 16(26), 3359-3380.
[http://dx.doi.org/10.2174/092986709789057653] [PMID: 19548867]
[37]
Da Pozzo, E.; Costa, B.; Martini, C. Translocator protein (TSPO) and neurosteroids: Implications in psychiatric disorders. Curr. Mol. Med., 2012, 12(4), 426-442.
[http://dx.doi.org/10.2174/156652412800163451] [PMID: 22348611]
[38]
Barresi, E.; Robello, M.; Costa, B.; Da Pozzo, E.; Baglini, E.; Salerno, S.; Da Settimo, F.; Martini, C.; Taliani, S. An update into the medicinal chemistry of translocator protein (TSPO) ligands. Eur. J. Med. Chem., 2021, 209, 112924.
[http://dx.doi.org/10.1016/j.ejmech.2020.112924] [PMID: 33081988]
[39]
Taliani, S.; Pugliesi, I.; Da Settimo, F. Structural requirements to obtain highly potent and selective 18 kDa Translocator Protein (TSPO). Ligands. Curr. Top. Med. Chem., 2011, 11(7), 860-886.
[http://dx.doi.org/10.2174/156802611795165142] [PMID: 21291396]
[40]
Scarf, A.M.; Ittner, L.M.; Kassiou, M. The translocator protein (18 kDa): Central nervous system disease and drug design. J. Med. Chem., 2009, 52(3), 581-592.
[http://dx.doi.org/10.1021/jm8011678] [PMID: 19133775]
[41]
Garnier, M.; Dimchev, A.B.; Boujrad, N.; Price, J.M.; Musto, N.A.; Papadopoulos, V. In vitro reconstitution of a functional peripheral-type benzodiazepine receptor from mouse Leydig tumor cells. Mol. Pharmacol., 1994, 45, 201-211.
[42]
Nguyen, N.; Fakra, E.; Pradel, V.; Jouve, E.; Alquier, C.; Le Guern, M.E.; Micallef, J.; Blin, O. Efficacy of etifoxine compared to lorazepam monotherapy in the treatment of patients with adjustment disorders with anxiety: A double-blind controlled study in general practice. Hum. Psychopharmacol. Clin. Exp., 2006, 21(3), 139-149.
[http://dx.doi.org/10.1002/hup.757]
[43]
Costa, B.; Cavallini, C.; Da Pozzo, E.; Taliani, S.; Da Settimo, F.; Martini, C. The anxiolytic etifoxine binds to TSPO Ro5-4864 binding site with long residence time showing a high neurosteroidogenic activity. ACS Chem. Neurosci., 2017, 8(7), 1448-1454.
[http://dx.doi.org/10.1021/acschemneuro.7b00027] [PMID: 28362078]
[44]
Kozikowski, A.P.; Ma, D.; Brewer, J.; Sun, S.; Costa, E.; Romeo, E.; Guidotti, A. Chemistry, binding affinities, and behavioral properties of a new class of “antineophobic” mitochondrial DBI receptor complex (mDRC) ligands. J. Med. Chem., 1993, 36(20), 2908-2920.
[http://dx.doi.org/10.1021/jm00072a010] [PMID: 8411007]
[45]
Primofiore, G.; Da Settimo, F.; Taliani, S.; Simorini, F.; Patrizi, M.P.; Novellino, E.; Greco, G.; Abignente, E.; Costa, B.; Chelli, B.; Martini, C.N. N-dialkyl-2-phenylindol-3-ylglyoxylamides. A new class of potent and selective ligands at the peripheral benzodiazepine receptor. J. Med. Chem., 2004, 47(7), 1852-1855.
[http://dx.doi.org/10.1021/jm030973k] [PMID: 15027878]
[46]
Da Settimo, F.; Simorini, F.; Taliani, S.; La Motta, C.; Marini, A.M.; Salerno, S.; Bellandi, M.; Novellino, E.; Greco, G.; Cosimelli, B.; Da Pozzo, E.; Costa, B.; Simola, N.; Morelli, M.; Martini, C. Anxiolytic-like effects of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides by modulation of translocator protein promoting neurosteroid biosynthesis. J. Med. Chem., 2008, 51(18), 5798-5806.
[http://dx.doi.org/10.1021/jm8003224] [PMID: 18729350]
[47]
Barresi, E.; Bruno, A.; Taliani, S.; Cosconati, S.; Da Pozzo, E.; Salerno, S.; Simorini, F.; Daniele, S.; Giacomelli, C.; Marini, A.M.; La Motta, C.; Marinelli, L.; Cosimelli, B.; Novellino, E.; Greco, G.; Da Settimo, F.; Martini, C. Deepening the topology of the translocator protein binding site by novel N,N-dialkyl-2-arylindol-3-ylglyoxylamides. J. Med. Chem., 2015, 58(15), 6081-6092.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00689] [PMID: 26177193]
[48]
Scarf, A.M.; Auman, K.M.; Kassiou, M. Is there any correlation between binding and functional effects at the translocator protein (TSPO) (18 kDa)? Curr. Mol. Med., 2012, 12(4), 387-397.
[http://dx.doi.org/10.2174/1566524011207040387] [PMID: 22348609]
[49]
Bruno, A.; Barresi, E.; Simola, N.; Da Pozzo, E.; Costa, B.; Novellino, E.; Da Settimo, F.; Martini, C.; Taliani, S.; Cosconati, S. Unbinding of translocator protein 18 kDa (TSPO) ligands: From in vitro residence time to in vivo efficacy via in silico simulations. ACS Chem. Neurosci., 2019, 10(8), 3805-3814.
[http://dx.doi.org/10.1021/acschemneuro.9b00300] [PMID: 31268683]
[50]
Okubo, T.; Yoshikawa, R.; Chaki, S.; Okuyama, S.; Nakazato, A. Design, synthesis and structure-affinity relationships of aryloxyanilide derivatives as novel peripheral benzodiazepine receptor ligands. Bioorg. Med. Chem., 2004, 12(2), 423-438.
[http://dx.doi.org/10.1016/j.bmc.2003.10.050] [PMID: 14723961]
[51]
Okuyama, S.; Chaki, S.; Yoshikawa, R.; Ogawa, S.; Suzuki, Y.; Okubo, T.; Nakazato, A.; Nagamine, M.; Tomisawa, K. Neuropharmacological profile of peripheral benzodiazepine receptor agonists, DAA1097 and DAA1106. Life Sci., 1999, 64(16), 1455-1464.
[http://dx.doi.org/10.1016/S0024-3205(99)00079-X] [PMID: 10321725]
[52]
Kim, T.; Yang, H.Y.; Park, B.G.; Jung, S.Y.; Park, J.H.; Park, K.D.; Min, S.J.; Tae, J.; Yang, H.; Cho, S.; Cho, S.J.; Song, H.; Mook-Jung, I.; Lee, J.; Pae, A.N. Discovery of benzimidazole derivatives as modulators of mitochondrial function: A potential treatment for Alzheimer’s disease. Eur. J. Med. Chem., 2017, 125, 1172-1192.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.017] [PMID: 27855359]
[53]
Ren, R.; Zhang, Y.; Li, B.; Wu, Y.; Li, B. Effect of β-amyloid (25-35) on mitochondrial function and expression of mitochondrial permeability transition pore proteins in rat hippocampal neurons. J. Cell. Biochem., 2011, 112(5), 1450-1457.
[http://dx.doi.org/10.1002/jcb.23062]
[54]
Halestrap, A.P. What is the mitochondrial permeability transition pore? J. Mol. Cell. Cardiol., 2009, 46(6), 821-831.
[http://dx.doi.org/10.1016/j.yjmcc.2009.02.021]
[55]
Bourguignon, J.J. Endogenous and synthetic ligands of mitochondrial benzodiazepine receptors: Structure-affinity relationships. In: Peripheral Benzodiazepine Receptors; GiesenCrouse, E., Ed.; Academic Press: London, 1993; p. 59, 85.
[56]
Trapani, G.; Franco, M.; Latrofa, A.; Ricciardi, L.; Carotti, A.; Serra, M.; Sanna, E.; Biggio, G.; Liso, G. Novel 2-phenylimidazo[1,2-a]pyridine derivatives as potent and selective ligands for peripheral benzodiazepine receptors: Synthesis, binding affinity, and in vivo studies. J. Med. Chem., 1999, 42(19), 3934-3941.
[http://dx.doi.org/10.1021/jm991035g] [PMID: 10508441]
[57]
Trapani, G.; Laquintana, V.; Denora, N.; Trapani, A.; Lopedota, A.; Latrofa, A.; Franco, M.; Serra, M.; Pisu, M.G.; Floris, I.; Sanna, E.; Biggio, G.; Liso, G. Structure-activity relationships and effects on neuroactive steroid synthesis in a series of 2-phenylimidazo[1,2-a]pyridineaceta-mide peripheral benzodiazepine receptors ligands. J. Med. Chem., 2005, 48(1), 292-305.
[http://dx.doi.org/10.1021/jm049610q] [PMID: 15634024]
[58]
Denora, N.; Laquintana, V.; Pisu, M.G.; Dore, R.; Murru, L.; Latrofa, A.; Trapani, G.; Sanna, E. 2-Phenyl-imidazo[1,2-a]pyridine compounds containing hydrophilic groups as potent and selective ligands for peripheral benzodiazepine receptors: Synthesis, binding affinity and electrophysiological studies. J. Med. Chem., 2008, 51(21), 6876-6888.
[http://dx.doi.org/10.1021/jm8006728] [PMID: 18834105]
[59]
Midzak, A.; Denora, N.; Laquintana, V.; Cutrignelli, A.; Lopedota, A.; Franco, M.; Altomare, C.D.; Papadopoulos, V. 2-Phenylimidazo[1,2-a]pyridine-containing ligands of the 18-kDa translocator protein (TSPO) behave as agonists and antagonists of steroidogenesis in a mouse leydig tumor cell line. Eur. J. Pharm. Sci., 2015, 76, 231-237.
[http://dx.doi.org/10.1016/j.ejps.2015.05.021] [PMID: 26002041]
[60]
Anzini, M.; Cappelli, A.; Vomero, S.; Giorgi, G.; Langer, T.; Bruni, G.; Romeo, M.R.; Basile, A.S. Molecular basis of peripheral vs central benzodiazepine receptor selectivity in a new class of peripheral benzodiazepine receptor ligands related to alpidem. J. Med. Chem., 1996, 39(21), 4275-4284.
[http://dx.doi.org/10.1021/jm960325j] [PMID: 8863805]
[61]
Cappelli, A.; Giuliani, G.; Valenti, S.; Anzini, M.; Vomero, S.; Giorgi, G.; Sogliano, C.; Maciocco, E.; Biggio, G.; Concas, A. Synthesis and structure-activity relationship studies in peripheral benzodiazepine receptor ligands related to alpidem. Bioorg. Med. Chem., 2008, 16(6), 3428-3437.
[http://dx.doi.org/10.1016/j.bmc.2007.06.044] [PMID: 18294852]
[62]
Vin, V.; Leducq, N.; Bono, F.; Herbert, J.M. Binding characteristics of SSR180575, a potent and selective peripheral benzodiazepine ligand. Biochem. Biophys. Res. Commun., 2003, 310(3), 785-790.
[http://dx.doi.org/10.1016/j.bbrc.2003.09.079] [PMID: 14550272]
[63]
Cappelli, A.; Bini, G.; Valenti, S.; Giuliani, G.; Paolino, M.; Anzini, M.; Vomero, S.; Giorgi, G.; Giordani, A.; Stasi, L.P.; Makovec, F.; Ghelardini, C.; Di Cesare Mannelli, L.; Concas, A.; Porcu, P.; Biggio, G. Synthesis and structure-activity relationship studies in translocator protein ligands based on a pyrazolo[3,4-b]quinoline scaffold. J. Med. Chem., 2011, 54(20), 7165-7175.
[http://dx.doi.org/10.1021/jm200770f] [PMID: 21916402]
[64]
Trapani, G.; Franco, M.; Ricciardi, L.; Latrofa, A.; Genchi, G.; Sanna, E.; Tuveri, F.; Cagetti, E.; Biggio, G.; Liso, G. Synthesis and binding affinity of 2-phenylimidazo[1,2-alpha]pyridine derivatives for both central and peripheral benzodiazepine receptors. A new series of high-affinity and selective ligands for the peripheral type. J. Med. Chem., 1997, 40(19), 3109-3118.
[http://dx.doi.org/10.1021/jm970112+] [PMID: 9301675]
[65]
Selleri, S.; Bruni, F.; Costagli, C.; Costanzo, A.; Guerrini, G.; Ciciani, G.; Costa, B.; Martini, C. 2-Arylpyrazolo[1,5-a]pyrimidin-3-yl acetamides. New potent and selective peripheral benzodiazepine receptor ligands. Bioorg. Med. Chem., 2001, 9(10), 2661-2671.
[http://dx.doi.org/10.1016/S0968-0896(01)00192-4] [PMID: 11557354]
[66]
Selleri, S.; Gratteri, P.; Costagli, C.; Bonaccini, C.; Costanzo, A.; Melani, F.; Guerrini, G.; Ciciani, G.; Costa, B.; Spinetti, F.; Martini, C.; Bruni, F. Insight into 2-phenylpyrazolo[1,5-a]pyrimidin-3-yl acetamides as peripheral benzodiazepine receptor ligands: Synthesis, biological evaluation and 3D-QSAR investigation. Bioorg. Med. Chem., 2005, 13(16), 4821-4834.
[http://dx.doi.org/10.1016/j.bmc.2005.05.015] [PMID: 15975799]
[67]
Reynolds, A.; Hanani, R.; Hibbs, D.; Damont, A.; Da Pozzo, E.; Selleri, S.; Dollé, F.; Martini, C.; Kassiou, M. Pyrazolo[1,5-a]pyrimidine acetamides: 4-Phenyl alkyl ether derivatives as potent ligands for the 18 kDa translocator protein (TSPO). Bioorg. Med. Chem. Lett., 2010, 20(19), 5799-5802.
[http://dx.doi.org/10.1016/j.bmcl.2010.07.135] [PMID: 20727749]
[68]
Tang, D.; McKinley, E.T.; Hight, M.R.; Uddin, M.I.; Harp, J.M.; Fu, A.; Nickels, M.L.; Buck, J.R.; Manning, H.C. Synthesis and structure-activity relationships of 5,6,7-substituted pyrazolopyrimidines: Discovery of a novel TSPO PET ligand for cancer imaging. J. Med. Chem., 2013, 56(8), 3429-3433.
[http://dx.doi.org/10.1021/jm4001874] [PMID: 23521048]
[69]
Banister, S.D.; Beinat, C.; Wilkinson, S.M.; Shen, B.; Bartoli, C.; Selleri, S.; Da Pozzo, E.; Martini, C.; Chin, F.T.; Kassiou, M. Ether analogues of DPA-714 with subnanomolar affinity for the translocator protein (TSPO). Eur. J. Med. Chem., 2015, 93, 392-400.
[http://dx.doi.org/10.1016/j.ejmech.2015.02.004] [PMID: 25725375]
[70]
Li, J.; Schulte, M.L.; Nickels, M.L.; Manning, H.C. New structure-activity relationships of N-acetamide substituted pyrazolopyrimidines as pharmacological ligands of TSPO. Bioorg. Med. Chem. Lett., 2016, 26(15), 3472-3477.
[http://dx.doi.org/10.1016/j.bmcl.2016.06.041] [PMID: 27353534]
[71]
Murata, T.; Masumoto, K.; Kondo, K. ; Furukawa, K Derives de 2-aryl-8-oxodihydropurine, procede de production de ces derives, compositions medicales contenant ces derives, et intermediaires de ces derives WO Patent 9928320, 1999.
[72]
Kita, A.; Kohayakawa, H.; Kinoshita, T.; Ochi, Y.; Nakamichi, K.; Kurumiya, S.; Furukawa, K.; Oka, M. Antianxiety and antidepressant-like effects of AC-5216, a novel mitochondrial benzodiazepine receptor ligand. Br. J. Pharmacol., 2004, 142(7), 1059-1072.
[http://dx.doi.org/10.1038/sj.bjp.0705681] [PMID: 15249420]
[73]
Mokrov, G.V.; Deeva, O.A.; Gudasheva, T.A.; Yarkov, S.A.; Yarkova, M.A.; Seredenin, S.B. Design, synthesis and anxiolytic-like activity of 1-arylpyrrolo[1,2-a]pyrazine-3-carboxamides. Bioorg. Med. Chem., 2015, 23(13), 3368-3378.
[http://dx.doi.org/10.1016/j.bmc.2015.04.049] [PMID: 25937237]
[74]
Bruhwyler, J.; Chleide, E.; Liégeois, J.F.; Delarge, J.; Mercier, M. Anxiolytic potential of sulpiride, clozapine and derivatives in the open-field test. Pharmacol. Biochem. Behav., 1990, 36(1), 57-61.
[http://dx.doi.org/10.1016/0091-3057(90)90125-2] [PMID: 2349269]
[75]
Yarkova, M.A.; Mokrov, G.V.; Gudasheva, T.A. Seredenin, SB Novel pyrrolo[1,2-a]pyrazines (TSPO ligands) with anxiolytic activity dependent on neurosteroid biosynthesis. Pharm. Chem. J., 2016, 50(8), 501-504.
[http://dx.doi.org/10.1007/s11094-016-1476-0]
[76]
Tallerova, A.V.; Mezhlumyan, A.G.; Yarkova, M.A.; Gudasheva, T.A.; Seredenin, S.B. Effects of original compounds GSB-106, GML-3, and GZK-111 in an experimental lipopolysaccharide-induced anhedonia model. Pharm. Chem. J., 2021, 55(2), 101-105.
[http://dx.doi.org/10.1007/s11094-021-02397-x]
[77]
Hallé, F.; Lejri, I.; Abarghaz, M.; Grimm, A.; Klein, C.; Maitre, M.; Schmitt, M.; Bourguignon, J.J.; Mensah-Nyagan, A.G.; Eckert, A.; Bihel, F. Discovery of imidazoquinazolinone derivatives as TSPO ligands modulating neurosteroidogenesis and cellular bioenergetics in neuroblastoma cells expressing amyloid precursor protein. ChemistrySelect, 2017, 2(22), 6452-6457.
[http://dx.doi.org/10.1002/slct.201701565]
[78]
Francis, J.E.; Cash, W.D.; Barbaz, B.S.; Bernard, P.S.; Lovell, R.A.; Mazzenga, G.C.; Friedmann, R.C.; Hyun, J.L.; Braunwalder, A.F.; Loo, P.S. Synthesis and benzodiazepine binding activity of a series of novel [1,2,4]triazolo[1,5-c]quinazolin-5(6H)-ones. J. Med. Chem., 1991, 34(1), 281-290.
[http://dx.doi.org/10.1021/jm00105a044] [PMID: 1846920]
[79]
Lejri, I.; Grimm, A.; Hallé, F.; Abarghaz, M.; Klein, C.; Maitre, M.; Schmitt, M.; Bourguignon, J.J.; Mensah-Nyagan, A.G.; Bihel, F.; Eckert, A. TSPO ligands boost mitochondrial function and pregnenolone synthesis. J. Alzheimers Dis., 2019, 72(4), 1045-1058.
[http://dx.doi.org/10.3233/JAD-190127] [PMID: 31256132]
[80]
Monga, S.; Denora, N.; Laquintana, V.; Franco, M.; Marek, I.; Singh, S.; Nagler, R.; Weizman, A.; Gavish, M. The protective effect of the TSPO ligands 2,4-Di-Cl-MGV-1, CB86, and CB204 against LPS-induced M1 pro-inflammatory activation of microglia. Brain Behav. Immun., 2020, 5, 100083.
[http://dx.doi.org/10.1016/j.bbih.2020.100083]
[81]
Vainshtein, A.; Veenman, L.; Shterenberg, A.; Singh, S.; Masarwa, A.; Dutta, B.; Island, B.; Tsoglin, E.; Levin, E.; Leschiner, S.; Maniv, I.; Pe’er, L.; Otradnov, I.; Zubedat, S.; Aga-Mizrachi, S.; Weizman, A.; Avital, A.; Marek, I.; Gavish, M. Quinazoline-based tricyclic compounds that regulate programmed cell death, induce neuronal differentiation, and are curative in animal models for excitotoxicity and hereditary brain disease. Cell Death Discov., 2015, 1(1), 15027.
[http://dx.doi.org/10.1038/cddiscovery.2015.27]
[82]
Azrad, M.; Zeineh, N.; Weizman, A.; Veenman, L.; Gavish, M. The TSPO ligands 2-Cl-MGV-1, MGV-1, and PK11195 differentially suppress the inflammatory response of BV-2 microglial cell to LPS. IJMS, 2019, 20(3), 594.
[http://dx.doi.org/10.3390/ijms20030594]
[83]
Gudasheva, T.A.; Deeva, O.A.; Mokrov, G.V.; Yarkov, S.A.; Yarkova, M.A.; Seredenin, S.B. The first dipeptide ligand of translocator protein: Design and anxiolytic activity. Dokl. Biochem. Biophys., 2015, 464(1), 290-293.
[http://dx.doi.org/10.1134/S1607672915050063] [PMID: 26518550]
[84]
Gudasheva, T.A. Theoretical grounds and technologies for dipeptide drug development. Russ. Chem. Bull., 2015, 64(9), 2012-2021.
[http://dx.doi.org/10.1007/s11172-015-1112-2]
[85]
Gudasheva, T.A.; Deeva, O.A.; Pantileev, A.S.; Mokrov, G.V.; Rybina, I.V.; Yarkova, M.A.; Seredenin, S.B. The new dipeptide TSPO ligands: Design, synthesis and structure–anxiolytic activity relationship. Molecules, 2020, 25(21), 5132.
[http://dx.doi.org/10.3390/molecules25215132]
[86]
Kim, T.; Morshed, M.N.; Londhe, A.M.; Lim, J.W.; Lee, H.E.; Cho, S.; Cho, S.J.; Hwang, H.; Lim, S.M.; Lee, J.Y.; Lee, J.; Pae, A.N. The translocator protein ligands as mitochondrial functional modulators for the potential anti-Alzheimer agents. J. Enzyme Inhib. Med. Chem., 2021, 36(1), 831-846.
[http://dx.doi.org/10.1080/14756366.2021.1900158]
[87]
McNeela, A.M.; Bernick, C.; Hines, R.M.; Hines, D.J. TSPO regulation in reactive gliotic diseases. J. Neurosci. Res., 2018, 96(6), 978-988.
[http://dx.doi.org/10.1002/jnr.24212] [PMID: 29315754]
[88]
Chen, Z.; Trapp, B.D. Microglia and neuroprotection. J. Neurochem., 2016, 136(Suppl. 1), 10-17.
[http://dx.doi.org/10.1111/jnc.13062] [PMID: 25693054]
[89]
Walker, D.G.; Lue, L.F. Immune phenotypes of microglia in human neurodegenerative disease: Challenges to detecting microglial polarization in human brains. Alzheimers Res. Ther., 2015, 7(1), 56.
[http://dx.doi.org/10.1186/s13195-015-0139-9] [PMID: 26286145]
[90]
Bae, K.R.; Shim, H.J.; Balu, D.; Kim, S.R.; Yu, S.W. Translocator protein 18 kDa negatively regulates inflammation in microglia. J. Neuroimmune Pharmacol., 2014, 9(3), 424-437.
[http://dx.doi.org/10.1007/s11481-014-9540-6] [PMID: 24687172]
[91]
Franco, R.; Fernández-Suárez, D. Alternatively activated microglia and macrophages in the central nervous system. Prog. Neurobiol., 2015, 131, 65-86.
[http://dx.doi.org/10.1016/j.pneurobio.2015.05.003] [PMID: 26067058]
[92]
Feng, H.; Liu, Y.; Zhang, R.; Liang, Y.; Sun, L.; Lan, N.; Ma, B. TSPO ligands PK11195 and Midazolam reduce NLRP3 inflammasome activation and proinflammatory cytokine release in BV-2 cells. Front. Cell. Neurosci., 2020, 14, 544431.
[http://dx.doi.org/10.3389/fncel.2020.544431] [PMID: 33362467]
[93]
Gavish, M.; Veenman, L.; Shterenberg, A.; Marek, I. Heterocyclic derivatives, pharmaceutical compounds, pharmaceutical compositions and methods of use thereof. US Patent 8541428B2, 2013.
[94]
Monga, S.; Nagler, R.; Amara, R.; Weizman, A.; Gavish, M. Inhibitory effects of the two novel TSPO ligands 2-Cl-MGV-1 and MGV-1 on LPS-induced microglial activation. Cells, 2019, 8(5), 486.
[http://dx.doi.org/10.3390/cells8050486] [PMID: 31121852]
[95]
Denora, N.; Iacobazzi, R.M.; Natile, G.; Margiotta, N. Metal complexes targeting the translocator protein 18kDa (TSPO). Coord. Chem. Rev., 2017, 341, 1-18.
[http://dx.doi.org/10.1016/j.ccr.2017.03.023]
[96]
Lee, J.W.; Nam, H.; Yu, S.W. Systematic analysis of translocator protein 18 kDa (TSPO) ligands on toll-like receptors-mediated pro-inflammatory responses in microglia and astrocytes. Exp. Neurobiol., 2016, 25(5), 262-268.
[http://dx.doi.org/10.5607/en.2016.25.5.262] [PMID: 27790060]
[97]
Dimitrova-Shumkovska, J.; Krstanoski, L.; Veenman, L. Diagnostic and therapeutic potential of TSPO studies regarding neurodegenerative diseases, psychiatric disorders, alcohol use disorders, traumatic brain injury, and stroke: An update. Cells, 2020, 9(4), 870.
[http://dx.doi.org/10.3390/cells9040870] [PMID: 32252470]
[98]
Midzak, A.; Papadopoulos, V. Adrenal mitochondria and steroidogenesis: From individual proteins to functional protein assemblies. Front. Endocrinol., 2016, 7, 106.
[http://dx.doi.org/10.3389/fendo.2016.00106]
[99]
Jia, K.; Du, H. Mitochondrial permeability transition: A pore intertwines brain aging and Alzheimer’s disease. Cells, 2021, 10(3), 649.
[http://dx.doi.org/10.3390/cells10030649] [PMID: 33804048]
[100]
Gavish, M.; Veenman, L. Regulation of mitochondrial, cellular, and organismal functions by TSPO. Adv. Pharmacol., 2018, 82, 103-136.
[http://dx.doi.org/10.1016/bs.apha.2017.09.004] [PMID: 29413517]
[101]
Liu, G-J.; Middleton, R.J.; Kam, W.W-Y.; Chin, D.Y.; Hatty, C.R.; Chan, R.H.Y.; Banati, R.B. Functional gains in energy and cell metabolism after TSPO gene insertion. Cell Cycle, 2017, 16(5), 436-447.
[http://dx.doi.org/10.1080/15384101.2017.1281477] [PMID: 28103132]
[102]
Bader, S.; Wolf, L.; Milenkovic, V.M.; Gruber, M.; Nothdurfter, C.; Rupprecht, R.; Wetzel, C.H. Differential effects of TSPO ligands on mitochondrial function in mouse microglia cells. Psychoneuroendocrinology, 2019, 106, 65-76.
[http://dx.doi.org/10.1016/j.psyneuen.2019.03.029] [PMID: 30954920]
[103]
Karlstetter, M.; Nothdurfter, C.; Aslanidis, A.; Moeller, K.; Horn, F.; Scholz, R.; Neumann, H.; Weber, B.H.; Rupprecht, R.; Langmann, T. Translocator protein (18 kDa) (TSPO) is expressed in reactive retinal microglia and modulates microglial inflammation and phagocytosis. J. Neuroinflammation, 2014, 11(1), 3.
[http://dx.doi.org/10.1186/1742-2094-11-3] [PMID: 24397957]
[104]
Pozzo, E.D.; Tremolanti, C.; Costa, B.; Giacomelli, C.; Milenkovic, V.M.; Bader, S.; Wetzel, C.H.; Rupprecht, R.; Taliani, S.; Settimo, F.D.; Martini, C. Microglial pro-inflammatory and anti-inflammatory phenotypes are modulated by translocator protein activation. Int. J. Mol. Sci., 2019, 20(18), 4467.
[http://dx.doi.org/10.3390/ijms20184467] [PMID: 31510070]
[105]
Germelli, L.; Da Pozzo, E.; Giacomelli, C.; Tremolanti, C.; Marchetti, L.; Wetzel, C.H.; Barresi, E.; Taliani, S.; Da Settimo, F.; Martini, C.; Costa, B. De novo neurosteroidogenesis in human microglia: Involvement of the 18 kDa translocator protein. Int. J. Mol. Sci., 2021, 22(6), 3115.
[http://dx.doi.org/10.3390/ijms22063115] [PMID: 33803741]
[106]
Garcia-Mesa, Y.; Jay, T.R.; Checkley, M.A.; Luttge, B.; Dobrowolski, C.; Valadkhan, S.; Landreth, G.E.; Karn, J.; Alvarez-Carbonell, D. Immortalization of primary microglia: A new platform to study HIV regulation in the central nervous system. J. Neurovirol., 2017, 23(1), 47-66.
[http://dx.doi.org/10.1007/s13365-016-0499-3] [PMID: 27873219]
[107]
Davis, R.L.; Buck, D.J.; McCracken, K.; Cox, G.W.; Das, S. Interleukin-1β-induced inflammatory signaling in C20 human microglial cells. Neuroimmunol. Neuroinflamm., 2018, 5, 50.
[http://dx.doi.org/10.20517/2347-8659.2018.60]
[108]
Santoro, A.; Mattace Raso, G.; Taliani, S.; Da Pozzo, E.; Simorini, F.; Costa, B.; Martini, C.; Laneri, S.; Sacchi, A.; Cosimelli, B.; Calignano, A.; Da Settimo, F.; Meli, R. TSPO-ligands prevent oxidative damage and inflammatory response in C6 glioma cells by neurosteroid synthesis. Eur. J. Pharm. Sci., 2016, 88, 124-131.
[http://dx.doi.org/10.1016/j.ejps.2016.04.006] [PMID: 27094781]
[109]
Arbo, B.D.; Marques, C.V.; Ruiz-Palmero, I.; Ortiz-Rodriguez, A.; Ghorbanpoor, S.; Arevalo, M.A.; Garcia-Segura, L.M.; Ribeiro, M.F. 4′-Chlorodiazepam is neuroprotective against amyloid-beta through the modulation of survivin and bax protein expression in vitro. Brain Res., 2016, 1632, 91-97.
[http://dx.doi.org/10.1016/j.brainres.2015.12.018] [PMID: 26707976]
[110]
Grimm, A.; Lejri, I.; Hallé, F.; Schmitt, M.; Götz, J.; Bihel, F.; Eckert, A. Mitochondria modulatory effects of new TSPO ligands in a cellular model of tauopathies. J. Neuroendocrinol., 2020, 32(1), e12796.
[http://dx.doi.org/10.1111/jne.12796] [PMID: 31536662]
[111]
Compston, A.; Coles, A. Multiple sclerosis. Lancet, 2008, 372(9648), 1502-1517.
[http://dx.doi.org/10.1016/S0140-6736(08)61620-7] [PMID: 18970977]
[112]
Filippi, M.; Bar-Or, A.; Piehl, F.; Preziosa, P.; Solari, A.; Vukusic, S.; Rocca, M.A. Author Correction: Multiple sclerosis. Nat. Rev. Dis. Primers, 2018, 4(1), 49.
[http://dx.doi.org/10.1038/s41572-018-0050-3]
[113]
Gholamzad, M.; Ebtekar, M.; Ardestani, M.S.; Azimi, M.; Mahmodi, Z.; Mousavi, M.J.; Aslani, S. A comprehensive review on the treatment approaches of multiple sclerosis: Currently and in the future. Inflamm. Res., 2019, 68(1), 25-38.
[http://dx.doi.org/10.1007/s00011-018-1185-0] [PMID: 30178100]
[114]
Kipp, M.; Nyamoya, S.; Hochstrasser, T.; Amor, S. Multiple sclerosis animal models: A clinical and histopathological perspective. Brain Pathol., 2017, 27(2), 123-137.
[http://dx.doi.org/10.1111/bpa.12454] [PMID: 27792289]
[115]
Noorbakhsh, F.; Ellestad, K.K.; Maingat, F.; Warren, K.G.; Han, M.H.; Steinman, L.; Baker, G.B.; Power, C. Impaired neurosteroid synthesis in multiple sclerosis. Brain, 2011, 134(Pt 9), 2703-2721.
[http://dx.doi.org/10.1093/brain/awr200] [PMID: 21908875]
[116]
Giatti, S.; Caruso, D.; Boraso, M.; Abbiati, F.; Ballarini, E.; Calabrese, D.; Pesaresi, M.; Rigolio, R.; Santos-Galindo, M.; Viviani, B.; Cavaletti, G.; Garcia-Segura, L.M.; Melcangi, R.C. Neuroprotective effects of progesterone in chronic experimental autoimmune encephalomyelitis. J. Neuroendocrinol., 2012, 24(6), 851-861.
[http://dx.doi.org/10.1111/j.1365-2826.2012.02284.x] [PMID: 22283602]
[117]
Yu, H.J.; Fei, J.; Chen, X.S.; Cai, Q.Y.; Liu, H.L.; Liu, G.D.; Yao, Z.X. Progesterone attenuates neurological behavioral deficits of experimental autoimmune encephalomyelitis through remyelination with nucleus-sublocalized Olig1 protein. Neurosci. Lett., 2010, 476(1), 42-45.
[http://dx.doi.org/10.1016/j.neulet.2010.03.079] [PMID: 20381586]
[118]
Garay, L.I.; González Deniselle, M.C.; Brocca, M.E.; Lima, A.; Roig, P.; De Nicola, A.F. Progesterone down-regulates spinal cord inflammatory mediators and increases myelination in experimental autoimmune encephalomyelitis. Neuroscience, 2012, 226, 40-50.
[http://dx.doi.org/10.1016/j.neuroscience.2012.09.032] [PMID: 23000619]
[119]
Panzica, G.C.; Balthazart, J.; Frye, C.A.; Garcia-Segura, L.M.; Herbison, A.E.; Mensah-Nyagan, A.G.; McCarthy, M.M.; Melcangi, R.C. Milestones on Steroids and the Nervous System: 10 years of basic and translational research. J. Neuroendocrinol., 2012, 24(1), 1-15.
[http://dx.doi.org/10.1111/j.1365-2826.2011.02265.x] [PMID: 22188420]
[120]
Porcu, P.; Barron, A.M.; Frye, C.A.; Walf, A.A.; Yang, S.Y.; He, X.Y.; Morrow, A.L.; Panzica, G.C.; Melcangi, R.C. Neurosteroidogenesis today: Novel targets for neuroactive steroid synthesis and action and their relevance for translational research. J. Neuroendocrinol., 2016, 28(2), 12351.
[http://dx.doi.org/10.1111/jne.12351] [PMID: 26681259]
[121]
Borowicz, K.K.; Piskorska, B.; Banach, M.; Czuczwar, S.J. Neuroprotective actions of neurosteroids. Front. Endocrinol. (Lausanne), 2011, 2, 50.
[http://dx.doi.org/10.3389/fendo.2011.00050] [PMID: 22649375]
[122]
Vowinckel, E.; Reutens, D.; Becher, B.; Verge, G.; Evans, A.; Owens, T.; Antel, J.P. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis. J. Neurosci. Res., 1997, 50(2), 345-353.
[http://dx.doi.org/10.1002/(SICI)1097-4547(19971015)50:2<345:AID-JNR22>3.0.CO;2-5] [PMID: 9373043]
[123]
Chechneva, O.V.; Deng, W. Mitochondrial translocator protein (TSPO), astrocytes and neuroinflammation. Neural Regen. Res., 2016, 11(7), 1056-1057.
[http://dx.doi.org/10.4103/1673-5374.187027] [PMID: 27630677]
[124]
Daugherty, D.J.; Selvaraj, V.; Chechneva, O.V.; Liu, X.B.; Pleasure, D.E.; Deng, W. A TSPO ligand is protective in a mouse model of multiple sclerosis. EMBO Mol. Med., 2013, 5(6), 891-903.
[http://dx.doi.org/10.1002/emmm.201202124] [PMID: 23681668]
[125]
Ravikumar, B.; Crawford, D.; Dellovade, T.; Savinainen, A.; Graham, D.; Liere, P.; Oudinet, J.P.; Webb, M.; Hering, H. Differential efficacy of the TSPO ligands etifoxine and XBD-173 in two rodent models of multiple sclerosis. Neuropharmacology, 2016, 108, 229-237.
[http://dx.doi.org/10.1016/j.neuropharm.2016.03.053] [PMID: 27039042]
[126]
Leva, G.; Klein, C.; Benyounes, J.; Hallé, F.; Bihel, F.; Collongues, N.; De Seze, J.; Mensah-Nyagan, A.G.; Patte-Mensah, C. The translocator protein ligand XBD173 improves clinical symptoms and neuropathological markers in the SJL/J mouse model of multiple sclerosis. Biochim. Biophys. Acta Mol. Basis Dis., 2017, 1863(12), 3016-3027.
[http://dx.doi.org/10.1016/j.bbadis.2017.09.007]
[127]
Nutma, E.; Stephenson, J.A.; Gorter, R.P.; de Bruin, J.; Boucherie, D.M.; Donat, C.K.; Breur, M.; van der Valk, P.; Matthews, P.M.; Owen, D.R.; Amor, S. A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis. Brain, 2019, 142(11), 3440-3455.
[http://dx.doi.org/10.1093/brain/awz287] [PMID: 31578541]
[128]
Guilarte, T.R. TSPO in diverse CNS pathologies and psychiatric disease: A critical review and a way forward. Pharmacol. Ther., 2019, 194, 44-58.
[http://dx.doi.org/10.1016/j.pharmthera.2018.09.003] [PMID: 30189290]
[129]
Lane, C.A.; Hardy, J.; Schott, J.M. Alzheimer’s disease. Eur. J. Neurol., 2018, 25(1), 59-70.
[http://dx.doi.org/10.1111/ene.13439] [PMID: 28872215]
[130]
Li, S.; Selkoe, D.J. A mechanistic hypothesis for the impairment of synaptic plasticity by soluble Aβ oligomers from Alzheimer’s brain. J. Neurochem., 2020, 154(6), 583-597.
[http://dx.doi.org/10.1111/jnc.15007] [PMID: 32180217]
[131]
Leng, F.; Edison, P. Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here? Nat. Rev. Neurol., 2021, 17(3), 157-172.
[http://dx.doi.org/10.1038/s41582-020-00435-y] [PMID: 33318676]
[132]
Chaney, A.; Williams, S.R.; Boutin, H. In vivo molecular imaging of neuroinflammation in Alzheimer’s disease. J. Neurochem., 2019, 149(4), 438-451.
[http://dx.doi.org/10.1111/jnc.14615] [PMID: 30339715]
[133]
Tournier, B.B.; Tsartsalis, S.; Ceyzériat, K.; Garibotto, V.; Millet, P. In vivo TSPO signal and neuroinflammation in Alzheimer’s disease. Cells, 2020, 9(9), 1941.
[http://dx.doi.org/10.3390/cells9091941] [PMID: 32839410]
[134]
Akwa, Y. Steroids and Alzheimer’s disease: Changes associated with pathology and therapeutic potential. Int. J. Mol. Sci., 2020, 21(13), 4812.
[http://dx.doi.org/10.3390/ijms21134812] [PMID: 32646017]
[135]
Ma, L.; Zhang, H.; Liu, N.; Wang, P.Q.; Guo, W.Z.; Fu, Q.; Jiao, L.B.; Ma, Y.Q.; Mi, W.D. TSPO ligand PK11195 alleviates neuroinflammation and beta-amyloid generation induced by systemic LPS administration. Brain Res. Bull., 2016, 121, 192-200.
[http://dx.doi.org/10.1016/j.brainresbull.2016.02.001] [PMID: 26851069]
[136]
Irwin, R.W.; Wang, J.M.; Chen, S.; Brinton, R.D. Neuroregenerative mechanisms of allopregnanolone in Alzheimer’s disease. Front. Endocrinol. (Lausanne), 2012, 2, 117.
[http://dx.doi.org/10.3389/fendo.2011.00117] [PMID: 22654847]
[137]
Oddo, S.; Caccamo, A.; Shepherd, J.D.; Murphy, M.P.; Golde, T.E.; Kayed, R.; Metherate, R.; Mattson, M.P.; Akbari, Y.; LaFerla, F.M. Triple-transgenic model of Alzheimer’s disease with plaques and tangles: Intracellular Abeta and synaptic dysfunction. Neuron, 2003, 39(3), 409-421.
[http://dx.doi.org/10.1016/S0896-6273(03)00434-3] [PMID: 12895417]
[138]
Barron, A.M.; Garcia-Segura, L.M.; Caruso, D.; Jayaraman, A.; Lee, J.W.; Melcangi, R.C.; Pike, C.J. Ligand for translocator protein reverses pathology in a mouse model of Alzheimer’s disease. J. Neurosci., 2013, 33(20), 8891-8897.
[http://dx.doi.org/10.1523/JNEUROSCI.1350-13.2013] [PMID: 23678130]
[139]
Christensen, A.; Pike, C.J. TSPO ligand PK11195 improves Alzheimer-related outcomes in aged female 3xTg-AD mice. Neurosci. Lett., 2018, 683, 7-12.
[http://dx.doi.org/10.1016/j.neulet.2018.06.029] [PMID: 29925037]
[140]
Christensen, A.; Pike, C.J. Age-dependent regulation of obesity and Alzheimer-related outcomes by hormone therapy in female 3xTg-AD mice. PLoS One, 2017, 12(6), e0178490.
[http://dx.doi.org/10.1371/journal.pone.0178490] [PMID: 28575011]
[141]
Fairley, L.H.; Sahara, N.; Aoki, I.; Ji, B.; Suhara, T.; Higuchi, M.; Barron, A.M. Neuroprotective effect of mitochondrial translocator protein ligand in a mouse model of tauopathy. J. Neuroinflammation, 2021, 18(1), 76.
[http://dx.doi.org/10.1186/s12974-021-02122-1] [PMID: 33740987]

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