Generic placeholder image

Current Medicinal Chemistry


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

Review Article

Recent Advances in the Development of Antidepressants Targeting the Purinergic P2X7 Receptor

Author(s): Shinyoung Lee, Hyunsoo Ha, Jaebong Jang and Youngjoo Byun*

Volume 30, Issue 2, 2023

Published on: 29 August, 2022

Page: [164 - 177] Pages: 14

DOI: 10.2174/0929867329666220629141418

Price: $65


The purinergic P2X7 receptor (P2X7R) is an adenosine triphosphate (ATP)- gated cation channel protein. Although extracellular ATP (eATP) is maintained at the nanomolar concentration range under normal conditions, it is elevated to micromolar levels in response to cell stress or damage, resulting in activation of P2X7R in the brain. The binding of eATP to P2X7R in glial cells in the brain activates the NLRP3 inflammasome and releases pro-inflammatory cytokines, such as IL-1β, IL-6, IL-18, and TNFα. Depression has been demonstrated to be strongly associated with neuroinflammation activated by P2X7R. Therefore, P2X7R is an attractive therapeutic target for depression. Multinational pharmaceutical companies, including AstraZeneca, GlaxoSmithKline, Janssen, Lundbeck, and Pfizer, have developed CNS-penetrating P2RX7 antagonists. Several of these have been evaluated in clinical trials. This review summarizes the recent development of P2X7R antagonists as novel antidepressant agents in terms of structural optimization, as well as in vitro/in vivo evaluation and physicochemical properties of representative compounds.

Keywords: Purinergic P2X7 receptor, depression, neuroinflammation, ATP, structure-activity relationship, BBB penetration.

WHO. Depression and other common mental disorders: Global health estimates. 2017. Available from:
Alcocer-Gómez, E.; Casas-Barquero, N.; Williams, M.R.; Romero-Guillena, S.L.; Cañadas-Lozano, D.; Bullón, P.; Sánchez-Alcazar, J.A.; Navarro-Pando, J.M.; Cordero, M.D. Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in major depressive disorder. Pharmacol. Res., 2017, 121, 114-121.
[] [PMID: 28465217]
US Food and Drug Administration Depression Medicines 2019. Available from:
Cipriani, A.; Furukawa, T.A.; Salanti, G.; Chaimani, A.; Atkinson, L.Z.; Ogawa, Y.; Leucht, S.; Ruhe, H.G.; Turner, E.H.; Higgins, J.P.T.; Egger, M.; Takeshima, N.; Hayasaka, Y.; Imai, H.; Shinohara, K.; Tajika, A.; Ioannidis, J.P.A.; Geddes, J.R. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: A systematic review and network meta-analysis. Lancet, 2018, 391(10128), 1357-1366.
[] [PMID: 29477251]
Al-Harbi, K.S. Treatment-resistant depression: Therapeutic trends, challenges, and future directions. Patient Prefer. Adherence, 2012, 6, 369-388.
[] [PMID: 22654508]
Grunebaum, M.F.; Galfalvy, H.C.; Choo, T.H.; Keilp, J.G.; Moitra, V.K.; Parris, M.S.; Marver, J.E.; Burke, A.K.; Milak, M.S.; Sublette, M.E.; Oquendo, M.A.; Mann, J.J. Ketamine for rapid reduction of suicidal thoughts in major depression: A midazolam-controlled randomized clinical trial. Am. J. Psychiatry, 2018, 175(4), 327-335.
[] [PMID: 29202655]
Murrough, J.W.; Iosifescu, D.V.; Chang, L.C.; Al Jurdi, R.K.; Green, C.E.; Perez, A.M.; Iqbal, S.; Pillemer, S.; Foulkes, A.; Shah, A.; Charney, D.S.; Mathew, S.J. Antidepressant efficacy of ketamine in treatment-resistant major depression: A two-site randomized controlled trial. Am. J. Psychiatry, 2013, 170(10), 1134-1142.
[] [PMID: 23982301]
Jauhar, S.; Morrison, P. Esketamine for treatment resistant depression. BMJ, 2019, 366, l5572.
[] [PMID: 31548292]
Rial, D.; Lemos, C.; Pinheiro, H.; Duarte, J.M.; Gonçalves, F.Q.; Real, J.I.; Prediger, R.D.; Gonçalves, N.; Gomes, C.A.; Canas, P.M.; Agostinho, P.; Cunha, R.A. Depression as a glial-based synaptic dysfunction. Front. Cell. Neurosci., 2016, 9, 521.
[] [PMID: 26834566]
Deussing, J.M.; Arzt, E. P2X7 receptor: A potential therapeutic target for depression? Trends Mol. Med., 2018, 24(9), 736-747.
[] [PMID: 30093269]
Illes, P.; Verkhratsky, A.; Tang, Y. Pathological ATPergic signaling in major depression and bipolar disorder. Front. Mol. Neurosci., 2020, 12, 331.
[] [PMID: 32076399]
Ribeiro, D.E.; Roncalho, A.L.; Glaser, T.; Ulrich, H.; Wegener, G.; Joca, S. P2X7 receptor signaling in stress and depression. Int. J. Mol. Sci., 2019, 20(11), E2778.
[] [PMID: 31174279]
Wei, L.; Syed Mortadza, S.A.; Yan, J.; Zhang, L.; Wang, L.; Yin, Y.; Li, C.; Chalon, S.; Emond, P.; Belzung, C.; Li, D.; Lu, C.; Roger, S.; Jiang, L.H. ATP-activated P2X7 receptor in the pathophysiology of mood disorders and as an emerging target for the development of novel antidepressant therapeutics. Neurosci. Biobehav. Rev., 2018, 87, 192-205.
[] [PMID: 29453990]
Nawazish-i-Husain Syed, C.K. Pharmacology of P2X receptors. Wiley Online Library, 2012.
Pasqualetto, G.; Brancale, A.; Young, M.T. The molecular determinants of small-molecule ligand binding at P2X receptors. Front. Pharmacol., 2018, 9, 58.
[] [PMID: 29456508]
Nelson, D.W.; Gregg, R.J.; Kort, M.E.; Perez-Medrano, A.; Voight, E.A.; Wang, Y.; Grayson, G.; Namovic, M.T.; Donnelly-Roberts, D.L.; Niforatos, W.; Honore, P.; Jarvis, M.F.; Faltynek, C.R.; Carroll, W.A. Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists. J. Med. Chem., 2006, 49(12), 3659-3666.
[] [PMID: 16759108]
McGaraughty, S.; Chu, K.L.; Namovic, M.T.; Donnelly-Roberts, D.L.; Harris, R.R.; Zhang, X.F.; Shieh, C.C.; Wismer, C.T.; Zhu, C.Z.; Gauvin, D.M.; Fabiyi, A.C.; Honore, P.; Gregg, R.J.; Kort, M.E.; Nelson, D.W.; Carroll, W.A.; Marsh, K.; Faltynek, C.R.; Jarvis, M.F. P2X7-related modulation of pathological nociception in rats. Neuroscience, 2007, 146(4), 1817-1828.
[] [PMID: 17478048]
Honore, P.; Donnelly-Roberts, D.; Namovic, M.; Zhong, C.; Wade, C.; Chandran, P.; Zhu, C.; Carroll, W.; Perez-Medrano, A.; Iwakura, Y.; Jarvis, M.F. The antihyperalgesic activity of a selective P2X7 receptor antagonist, A-839977, is lost in IL-1alphabeta knockout mice. Behav. Brain Res., 2009, 204(1), 77-81.
[] [PMID: 19464323]
Honore, P.; Donnelly-Roberts, D.; Namovic, M.T.; Hsieh, G.; Zhu, C.Z.; Mikusa, J.P.; Hernandez, G.; Zhong, C.; Gauvin, D.M.; Chandran, P.; Harris, R.; Medrano, A.P.; Carroll, W.; Marsh, K.; Sullivan, J.P.; Faltynek, C.R.; Jarvis, M.F. A-740003 [N-(1-[(cyanoimino)(5-quinolinylamino) methyl]amino-2,2-dimethylpropyl)-2-(3,4-dimeth- oxyphenyl)acetamide], a novel and selective P2X7 receptor antagonist, dose-dependently reduces neuropathic pain in the rat. J. Pharmacol. Exp. Ther., 2006, 319(3), 1376-1385.
[] [PMID: 16982702]
Zhang, X.F.; Han, P.; Faltynek, C.R.; Jarvis, M.F.; Shieh, C.C. Functional expression of P2X7 receptors in non-neuronal cells of rat dorsal root ganglia. Brain Res., 2005, 1052(1), 63-70.
[] [PMID: 16005856]
Janssen, B.; Vugts, D.J.; Funke, U.; Spaans, A.; Schuit, R.C.; Kooijman, E.; Rongen, M.; Perk, L.R.; Lammertsma, A.A.; Windhorst, A.D. Synthesis and initial preclinical evaluation of the P2X7 receptor antagonist [¹¹C]A-740003 as a novel tracer of neuroinflammation. J. Labelled Compd. Rad., 2014, 57(8), 509-516.
[] [PMID: 24995673]
Bhattacharya, A.; Wang, Q.; Ao, H.; Shoblock, J.R.; Lord, B.; Aluisio, L.; Fraser, I.; Nepomuceno, D.; Neff, R.A.; Welty, N.; Lovenberg, T.W.; Bonaventure, P.; Wickenden, A.D.; Letavic, M.A. Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567. Br. J. Pharmacol., 2013, 170(3), 624-640.
[] [PMID: 23889535]
Anderson, C.M.; Nedergaard, M. Emerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons. Trends Neurosci., 2006, 29(5), 257-262.
[] [PMID: 16564580]
Iwata, M.; Ota, K.T.; Li, X.Y.; Sakaue, F.; Li, N.; Dutheil, S.; Banasr, M.; Duric, V.; Yamanashi, T.; Kaneko, K.; Rasmussen, K.; Glasebrook, A.; Koester, A.; Song, D.; Jones, K.A.; Zorn, S.; Smagin, G.; Duman, R.S. Psychological stress activates the inflammasome via release of adenosine triphosphate and stimulation of the purinergic type 2X7 Receptor. Biol. Psychiatry, 2016, 80(1), 12-22.
[] [PMID: 26831917]
Donnelly-Roberts, D.L.; Namovic, M.T.; Surber, B.; Vaidyanathan, S.X.; Perez-Medrano, A.; Wang, Y.; Carroll, W.A.; Jarvis, M.F. [3H]A-804598 ([3H]2-cyano-1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine) is a novel, potent, and selective antagonist radioligand for P2X7 receptors. Neuropharmacology, 2009, 56(1), 223-229.
[] [PMID: 18602931]
Csölle, C.; Baranyi, M.; Zsilla, G.; Kittel, A.; Gölöncsér, F.; Illes, P.; Papp, E.; Vizi, E.S.; Sperlágh, B. Neurochemical changes in the mouse hippocampus underlying the antidepressant effect of genetic deletion of P2X7 receptors. PLoS One, 2013, 8(6), e66547.
[] [PMID: 23805233]
Hopper, A.T.; Juhl, M.; Hornberg, J.; Badolo, L.; Kilburn, J.P.; Thougaard, A.; Smagin, G.; Song, D.; Calice, L.; Menon, V.; Dale, E.; Zhang, H.; Cajina, M.; Nattini, M.E.; Gandhi, A.; Grenon, M.; Jones, K.; Khayrullina, T.; Chandrasena, G.; Thomsen, C.; Zorn, S.H.; Brodbeck, R.; Poda, S.B.; Staal, R.; Möller, T. Synthesis and characterization of the novel rodent-active and CNS-Penetrant P2X7 receptor antagonist Lu AF27139. J. Med. Chem., 2021, 64(8), 4891-4902.
[] [PMID: 33822617]
Keystone, E.C.; Wang, M.M.; Layton, M.; Hollis, S.; McInnes, I.B.; Team, D.C.S. Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active disease despite treatment with methotrexate or sulphasalazine. Ann. Rheum. Dis., 2012, 71(10), 1630-1635.
[] [PMID: 22966146]
Eser, A.; Colombel, J.F.; Rutgeerts, P.; Vermeire, S.; Vogelsang, H.; Braddock, M.; Persson, T.; Reinisch, W. Safety and efficacy of an oral inhibitor of the purinergic receptor P2X7 in adult patients with moderately to severely active crohn’s disease: A randomized placebo-controlled, double-blind, phase IIa study. Inflamm. Bowel Dis., 2015, 21(10), 2247-2253.
[] [PMID: 26197451]
Stokes, L.; Jiang, L.H.; Alcaraz, L.; Bent, J.; Bowers, K.; Fagura, M.; Furber, M.; Mortimore, M.; Lawson, M.; Theaker, J.; Laurent, C.; Braddock, M.; Surprenant, A. Characterization of a selective and potent antagonist of human P2X(7) receptors, AZ11645373. Br. J. Pharmacol., 2006, 149(7), 880-887.
[] [PMID: 17031385]
Rosli, S.; Kirby, F.J.; Lawlor, K.E.; Rainczuk, K.; Drummond, G.R.; Mansell, A.; Tate, M.D. Repurposing drugs targeting the P2X7 receptor to limit hyperinflammation and disease during influenza virus infection. Br. J. Pharmacol., 2019, 176(19), 3834-3844.
[] [PMID: 31271646]
Chambers, L.J.; Stevens, A.J.; Moses, A.P.; Michel, A.D.; Walter, D.S.; Davies, D.J.; Livermore, D.G.; Fonfria, E.; Demont, E.H.; Vimal, M.; Theobald, P.J.; Beswick, P.J.; Gleave, R.J.; Roman, S.A.; Senger, S. Synthesis and structure-activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor. Bioorg. Med. Chem. Lett., 2010, 20(10), 3161-3164.
[] [PMID: 20399651]
Beswick, P.J.; Billinton, A.; Chambers, L.J.; Dean, D.K.; Fonfria, E.; Gleave, R.J.; Medhurst, S.J.; Michel, A.D.; Moses, A.P.; Patel, S.; Roman, S.A.; Roomans, S.; Senger, S.; Stevens, A.J.; Walter, D.S. Structure-activity relationships and in vivo activity of (1H-pyrazol-4-yl)acetamide antagonists of the P2X(7) receptor. Bioorg. Med. Chem. Lett., 2010, 20(15), 4653-4656.
[] [PMID: 20579878]
Abdi, M.H.; Beswick, P.J.; Billinton, A.; Chambers, L.J.; Charlton, A.; Collins, S.D.; Collis, K.L.; Dean, D.K.; Fonfria, E.; Gleave, R.J.; Lejeune, C.L.; Livermore, D.G.; Medhurst, S.J.; Michel, A.D.; Moses, A.P.; Page, L.; Patel, S.; Roman, S.A.; Senger, S.; Slingsby, B.; Steadman, J.G.; Stevens, A.J.; Walter, D.S. Discovery and structure-activity relationships of a series of pyroglutamic acid amide antagonists of the P2X7 receptor. Bioorg. Med. Chem. Lett., 2010, 20(17), 5080-5084.
[] [PMID: 20673717]
Abberley, L.; Bebius, A.; Beswick, P.J.; Billinton, A.; Collis, K.L.; Dean, D.K.; Fonfria, E.; Gleave, R.J.; Medhurst, S.J.; Michel, A.D.; Moses, A.P.; Patel, S.; Roman, S.A.; Scoccitti, T.; Smith, B.; Steadman, J.G.A.; Walter, D.S. Identification of 2-oxo-N-(phenylmethyl)-4-imidazolidinecarboxamide antagonists of the P2X(7) receptor. Bioorg. Med. Chem. Lett., 2010, 20(22), 6370-6374.
[] [PMID: 20934331]
Ali, Z.; Laurijssens, B.; Ostenfeld, T.; McHugh, S.; Stylianou, A.; Scott-Stevens, P.; Hosking, L.; Dewit, O.; Richardson, J.C.; Chen, C. Pharmacokinetic and pharmacodynamic profiling of a P2X7 receptor allosteric modulator GSK1482160 in healthy human subjects. Br. J. Clin. Pharmacol., 2013, 75(1), 197-207.
[] [PMID: 22568863]
Letavic, M.A.; Lord, B.; Bischoff, F.; Hawryluk, N.A.; Pieters, S.; Rech, J.C.; Sales, Z.; Velter, A.I.; Ao, H.; Bonaventure, P.; Contreras, V.; Jiang, X.; Morton, K.L.; Scott, B.; Wang, Q.; Wickenden, A.D.; Carruthers, N.I.; Bhattacharya, A. Synthesis and pharmacological characterization of two novel, brain penetrating P2X7 antagonists. ACS Med. Chem. Lett., 2013, 4(4), 419-422.
[] [PMID: 24900687]
Lord, B.; Aluisio, L.; Shoblock, J.R.; Neff, R.A.; Varlinskaya, E.I.; Ceusters, M.; Lovenberg, T.W.; Carruthers, N.; Bonaventure, P.; Letavic, M.A.; Deak, T.; Drinkenburg, W.; Bhattacharya, A. Pharmacology of a novel central nervous system-penetrant P2X7 antagonist JNJ-42253432. J. Pharmacol. Exp. Ther., 2014, 351(3), 628-641.
[] [PMID: 25271258]
Swanson, D.M.; Savall, B.M.; Coe, K.J.; Schoetens, F.; Koudriakova, T.; Skaptason, J.; Wall, J.; Rech, J.; Deng, X.; De Angelis, M.; Everson, A.; Lord, B.; Wang, Q.; Ao, H.; Scott, B.; Sepassi, K.; Lovenberg, T.W.; Carruthers, N.I.; Bhattacharya, A.; Letavic, M.A. Identification of (R)-(2-Chloro-3-(trifluoromethyl)phenyl)(1-(5-fluoropyridin-2-yl)-4-methyl-6,7-dihydro-1H-imidazo[4,5-c]pyridin-5(4H)-yl)methanone (JNJ 54166060), a small molecule antagonist of the P2X7 receptor. J. Med. Chem., 2016, 59(18), 8535-8548.
[] [PMID: 27548392]
Lord, B.; Ameriks, M.K.; Wang, Q.; Fourgeaud, L.; Vliegen, M.; Verluyten, W.; Haspeslagh, P.; Carruthers, N.I.; Lovenberg, T.W.; Bonaventure, P.; Letavic, M.A.; Bhattacharya, A. A novel radioligand for the ATP-gated ion channel P2X7: [3H] JNJ-54232334. Eur. J. Pharmacol., 2015, 765, 551-559.
[] [PMID: 26386289]
Letavic, M.A.; Savall, B.M.; Allison, B.D.; Aluisio, L.; Andres, J.I.; De Angelis, M.; Ao, H.; Beauchamp, D.A.; Bonaventure, P.; Bryant, S.; Carruthers, N.I.; Ceusters, M.; Coe, K.J.; Dvorak, C.A.; Fraser, I.C.; Gelin, C.F.; Koudriakova, T.; Liang, J.; Lord, B.; Lovenberg, T.W.; Otieno, M.A.; Schoetens, F.; Swanson, D.M.; Wang, Q.; Wickenden, A.D.; Bhattacharya, A. 4-Methyl-6,7-dihydro-4H-triazolo[4,5-c]pyridine-Based P2X7 receptor antagonists: Optimization of pharmacokinetic properties leading to the identification of a clinical candidate. J. Med. Chem., 2017, 60(11), 4559-4572.
[] [PMID: 28493698]
Recourt, K.; van der Aart, J.; Jacobs, G.; de Kam, M.; Drevets, W.; van Nueten, L.; Kanhai, K.; Siebenga, P.; Zuiker, R.; Ravenstijn, P.; Timmers, M.; van Gerven, J.; de Boer, P. Characterisation of the pharmacodynamic effects of the P2X7 receptor antagonist JNJ-54175446 using an oral dexamphetamine challenge model in healthy males in a randomised, double-blind, placebo-controlled, multiple ascending dose trial. J. Psychopharmacol., 2020, 34(9), 1030-1042.
[] [PMID: 32248747]
Timmers, M.; Ravenstijn, P.; Xi, L.; Triana-Baltzer, G.; Furey, M.; Van Hemelryck, S.; Biewenga, J.; Ceusters, M.; Bhattacharya, A.; van den Boer, M.; van Nueten, L.; de Boer, P. Clinical pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-54175446, a brain permeable P2X7 antagonist, in a randomised single-ascending dose study in healthy participants. J. Psychopharmacol., 2018, 32(12), 1341-1350.
[] [PMID: 30260294]
Bhattacharya, A.; Lord, B.; Grigoleit, J.S.; He, Y.; Fraser, I.; Campbell, S.N.; Taylor, N.; Aluisio, L.; O’Connor, J.C.; Papp, M.; Chrovian, C.; Carruthers, N.; Lovenberg, T.W.; Letavic, M.A. Neuropsychopharmacology of JNJ-55308942: Evaluation of a clinical candidate targeting P2X7 ion channels in animal models of neuroinflammation and anhedonia. Neuropsychopharmacology, 2018, 43(13), 2586-2596.
[] [PMID: 30026598]
Chrovian, C.C.; Soyode-Johnson, A.; Peterson, A.A.; Gelin, C.F.; Deng, X.; Dvorak, C.A.; Carruthers, N.I.; Lord, B.; Fraser, I.; Aluisio, L.; Coe, K.J.; Scott, B.; Koudriakova, T.; Schoetens, F.; Sepassi, K.; Gallacher, D.J.; Bhattacharya, A.; Letavic, M.A. A dipolar cycloaddition reaction to access 6-Methyl-4,5,6,7-tetrahydro-1H-[1,2,3]triazolo[4,5-c]pyridines enables the discovery synthesis and preclinical profiling of a P2X7 antagonist clinical candidate. J. Med. Chem., 2018, 61(1), 207-223.
[] [PMID: 29211470]
Paul, J.; Lars, K.; Rasmussen, K.; Jessing, M.; Eldemenky, M.E.; Jiang, Y.; Chen, B. cyclic Amines. Patent WO2014057080A2, 2014.
Duplantier, A.J.; Dombroski, M.A.; Subramanyam, C.; Beaulieu, A.M.; Chang, S.P.; Gabel, C.A.; Jordan, C.; Kalgutkar, A.S.; Kraus, K.G.; Labasi, J.M.; Mussari, C.; Perregaux, D.G.; Shepard, R.; Taylor, T.J.; Trevena, K.A.; Whitney-Pickett, C.; Yoon, K. Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224,535. Bioorg. Med. Chem. Lett., 2011, 21(12), 3708-3711.
[] [PMID: 21565499]
Stock, T.C.; Bloom, B.J.; Wei, N.; Ishaq, S.; Park, W.; Wang, X.; Gupta, P.; Mebus, C.A. Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate. J. Rheumatol., 2012, 39(4), 720-727.
[] [PMID: 22382341]
Calzaferri, F.; Narros-Fernández, P.; de Pascual, R.; de Diego, A.M.G.; Nicke, A.; Egea, J.; García, A.G.; de Los Ríos, C. Synthesis and pharmacological evaluation of novel non-nucleotide purine derivatives as P2X7 antagonists for the treatment of neuroinflammation. J. Med. Chem., 2021, 64(4), 2272-2290.
[] [PMID: 33560845]
Pajouhesh, H.; Lenz, G.R. Medicinal chemical properties of successful central nervous system drugs. NeuroRx, 2005, 2(4), 541-553.
[] [PMID: 16489364]
Guntner, A.S.; Bögl, T.; Mlynek, F.; Buchberger, W. Large-scale evaluation of collision cross sections to investigate blood-brain barrier permeation of drugs. Pharmaceutics, 2021, 13(12), 2141.
[] [PMID: 34959422]
Karasawa, A.; Kawate, T. Structural basis for subtype-specific inhibition of the P2X7 receptor. eLife, 2016, 5, 5.
[] [PMID: 27935479]
Schotten, M.T. Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Struct. Funct., 2008, 213, 93-118.
[] [PMID: 18704495]
Dantzer, R. Neuroimmune interactions: From the brain to the immune system and vice versa. Physiol. Rev., 2018, 98(1), 477-504.
[] [PMID: 29351513]
Wingo, T.S.; Liu, Y.; Gerasimov, E.S.; Gockley, J.; Logsdon, B.A.; Duong, D.M.; Dammer, E.B.; Lori, A.; Kim, P.J.; Ressler, K.J.; Beach, T.G.; Reiman, E.M.; Epstein, M.P.; De Jager, P.L.; Lah, J.J.; Bennett, D.A.; Seyfried, N.T.; Levey, A.I.; Wingo, A.P. Brain proteome-wide association study implicates novel proteins in depression pathogenesis. Nat. Neurosci., 2021, 24(6), 810-817.
[] [PMID: 33846625]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy