Generic placeholder image

Current Medicinal Chemistry

Author(s): Marcos Martínez-Banaclocha*

DOI: 10.2174/0929867326666191015091346

DownloadDownload PDF Flyer Cite As
N-acetyl-cysteine in Schizophrenia: Potential Role on the Sensitive Cysteine Proteome

Page: [6424 - 6439] Pages: 16

  • * (Excluding Mailing and Handling)

Abstract

Background: N-acetyl-cysteine (NAC) has shown widespread utility in different psychiatric disorders, including a beneficial role in schizophrenic patients. Although the replenishment of glutathione and the antioxidant activity of NAC have been suggested as the mechanisms that improve such a wide range of disorders, none seems to be sufficiently specific to explain these intriguing effects. A sensitive cysteine proteome is emerging as a functional and structural network of interconnected Sensitive Cysteine-containing Proteins (SCCPs) that together with reactive species and the cysteine/ glutathione cycles can regulate the bioenergetic metabolism, the redox homeostasis and the cellular growth, differentiation and survival, acting through different pathways that are regulated by the same thiol radical in cysteine residues.

Objective: Since this sensitive cysteine network has been implicated in the pathogenesis of Parkinson’s and Alzheimer's diseases, I have reviewed if the proteins that play a role in schizophrenia can be classified as SCCPs.

Results: The results show that the principal proteins playing a role in schizophrenia can be classified as SCCPs, suggesting that the sensitive cysteine proteome (cysteinet) is defective in this type of psychosis.

Conclusion: The present review proposes that there is a deregulation of the sensitive cysteine proteome in schizophrenia as the consequence of a functional imbalance among different SCCPs, which play different functions in neurons and glial cells. In this context, the role of NAC to restore and prevent schizophrenic disorders is discussed.

Keywords: Cysteine, thiol, reactive species, N-acetyl-cysteine, cysteinet, schizophrenia, cysteine proteome.

[1]
Saha, S.; Chant, D.; Welham, J.; McGrath, J. A systematic review of the prevalence of schizophrenia. PLoS Med., 2005, 2(5), e141.
[http://dx.doi.org/10.1371/journal.pmed.0020141 ] [PMID: 15916472]
[2]
Berry, N.; Jobanputra, V.; Pal, H. Molecular genetics of schizophrenia: a critical review. J. Psychiatry Neurosci., 2003, 28(6), 415-429.
[PMID: 14631454]
[3]
Avramopoulos, D. Recent advances in the genetics of schizophrenia. Mol. Neuropsychiatry, 2018, 4(1), 35-51.
[http://dx.doi.org/10.1159/000488679 ] [PMID: 29998117]
[4]
Shepherd, A.M.; Laurens, K.R.; Matheson, S.L.; Carr, V.J.; Green, M.J. Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia. Neurosci. Biobehav. Rev., 2012, 36(4), 1342-1356.
[http://dx.doi.org/10.1016/j.neubiorev.2011.12.015 ] [PMID: 22244985]
[5]
Rund, B.R. The research evidence for schizophrenia as a neurodevelopmental disorder. Scand. J. Psychol., 2018, 59(1), 49-58.
[http://dx.doi.org/10.1111/sjop.12414 ] [PMID: 29356007]
[6]
Rapoport, J.L.; Giedd, J.N.; Gogtay, N. Neurodevelopmental model of schizophrenia: update 2012. Mol. Psychiatry, 2012, 17(12), 1228-1238.
[http://dx.doi.org/10.1038/mp.2012.23 ] [PMID: 22488257]
[7]
Patel, K.R.; Cherian, J.; Gohil, K.; Atkinson, D. Schizophrenia: overview and treatment options. P&T, 2014, 39(9), 638-645.
[PMID: 25210417]
[8]
Baker, J.T.; Holmes, A.J.; Masters, G.A.; Yeo, B.T.; Krienen, F.; Buckner, R.L.; Öngür, D. Disruption of cortical association networks in schizophrenia and psychotic bipolar disorder. JAMA Psychiatry, 2014, 71(2), 109-118.
[http://dx.doi.org/10.1001/jamapsychiatry.2013.3469 ] [PMID: 24306091]
[9]
Schifani, C.; Tseng, H-H.; Kenk, M.; Tagore, A.; Kiang, M.; Wilson, A.A.; Houle, S.; Rusjan, P.M.; Mizrahi, R. Cortical stress regulation is disrupted in schizophrenia but not in clinical high risk for psychosis. Brain, 2018, 141(7), 2213-2224.
[http://dx.doi.org/10.1093/brain/awy133 ] [PMID: 29860329]
[10]
Zalesky, A.; Fornito, A.; Seal, M.L.; Cocchi, L.; Westin, C.F.; Bullmore, E.T.; Egan, G.F.; Pantelis, C. Disrupted axonal fiber connectivity in schizophrenia. Biol. Psychiatry, 2011, 69(1), 80-89.
[http://dx.doi.org/10.1016/j.biopsych.2010.08.022 ] [PMID: 21035793]
[11]
Davalieva, K.; Maleva Kostovska, I.; Dwork, A.J. Proteomics research in schizophrenia. Front. Cell. Neurosci., 2016, 10, 18.
[http://dx.doi.org/10.3389/fncel.2016.00018 ] [PMID: 26909022]
[12]
Nascimento, J.M.; Martins-de-Souza, D. The proteome of schizophrenia. NPJ Schizophr., 2015, 1, 14003.
[http://dx.doi.org/10.1038/npjschz.2014.3 ] [PMID: 27336025]
[13]
Zheng, W.; Zhang, Q.E.; Cai, D.B.; Yang, X.H.; Qiu, Y.; Ungvari, G.S.; Ng, C.H.; Berk, M.; Ning, Y.P.; Xiang, Y.T. N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials. Acta Psychiatr. Scand., 2018, 137(5), 391-400.
[http://dx.doi.org/10.1111/acps.12862 ] [PMID: 29457216]
[14]
Ooi, S.L.; Green, R.; Pak, S.C. N-Acetylcysteine for the treatment of psychiatric disorders: a review of current evidence. BioMed Res. Int., 2018, 2018, 2469486.
[http://dx.doi.org/10.1155/2018/2469486 ] [PMID: 30426004]
[15]
Dean, O.; Giorlando, F.; Berk, M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J. Psychiatry Neurosci., 2011, 36(2), 78-86.
[http://dx.doi.org/10.1503/jpn.100057 ] [PMID: 21118657]
[16]
Rossell, S.L.; Francis, P.S.; Galletly, C.; Harris, A.; Siskind, D.; Berk, M.; Bozaoglu, K.; Dark, F.; Dean, O.; Liu, D.; Meyer, D.; Neill, E.; Phillipou, A.; Sarris, J.; Castle, D.J. N-acetylcysteine (NAC) in schizophrenia resistant to clozapine: a double blind randomised placebo controlled trial targeting negative symptoms. BMC Psychiatry, 2016, 16(1), 320.
[http://dx.doi.org/10.1186/s12888-016-1030-3 ] [PMID: 27629871]
[17]
Deepmala, D.; Slattery, J.; Kumar, N.; Delhey, L.; Berk, M.; Dean, O.; Spielholz, C.; Frye, R. Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review. Neurosci. Biobehav. Rev., 2015, 55, 294-321.
[http://dx.doi.org/10.1016/j.neubiorev.2015.04.015 ] [PMID: 25957927]
[18]
Martinez-Banaclocha, M. Cellular cysteine network (CYSTEINET): pharmacological intervention in brain aging and neurodegenerative diseases in: Frontiers in clinical drug research-central nervous system. Atta-ur-Rahman (Ed.); Bentham Science Publisher,, 2016, 2, pp. 105-172.
[http://dx.doi.org/10.2174/9781681081892116020004]
[19]
Mollica, A.; Feliciani, F.; Stefanucci, A.; Cacciatore, I.; Cornacchia, C.; Torino, D.; Pinnen, F.N. -(tert)-butyloxycarbonyl)-beta,beta-cyclopentyl-cysteine (acetamidomethyl)-methyl ester for synthesis of novel peptidomimetic derivatives. Protein Pept. Lett., 2010, 17(7), 925-929.
[http://dx.doi.org/10.2174/092986610791306760 ] [PMID: 20205656]
[20]
Cacciatore, I.; Cornacchia, C.; Baldassarre, L.; Fornasari, E.; Mollica, A.; Stefanucci, A.; Pinnen, F. GPE and GPE analogues as promising neuroprotective agents. Mini Rev. Med. Chem., 2012, 12(1), 13-23.
[http://dx.doi.org/10.2174/138955712798868995 ] [PMID: 22070686]
[21]
Stefanucci, A.; Costante, R.; Macedonio, G. Cysteine-, methionine- and seleno-cysteine-proline chimeras: synthesis and their use in peptidomimetics design. Curr. Bioact. Compd., 2016, 12, 200.
[http://dx.doi.org/10.2174/1573407212666160511162915]
[22]
Go, Y-M.; Jones, D.P. The redox proteome. J. Biol. Chem., 2013, 288(37), 26512-26520.
[http://dx.doi.org/10.1074/jbc.R113.464131 ] [PMID: 23861437]
[23]
Martinez-Banaclocha, M. N-acetylcysteine in psychiatric disorders: possible role of cysteinet deregulation. Inter. Neuropsy. Dis. J., 2018, 12, 1-6.
[http://dx.doi.org/10.9734/INDJ/2018/44483]
[24]
Martínez-Banaclocha, M. Cysteine network (CYSTEINET) dysregulation in Parkinson’s disease: role of N-acetylcysteine. Curr. Drug Metab., 2016, 17(4), 368-385.
[http://dx.doi.org/10.2174/1389200217666151210125918 ] [PMID: 26651975]
[25]
Martinez-Banaclocha, M. N-acetylcysteine: A natural antidote for Alzheimer’s disease. Alzheimer Dis. Dement., 2016, 1, 4-15.
[http://dx.doi.org/10.36959/734/367 ]
[26]
Petrova, B.; Liu, K.; Tian, C.; Kitaoka, M.; Freinkman, E.; Yang, J.; Orr-Weaver, T.L. Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes. Proc. Natl. Acad. Sci. USA, 2018, 115(34), E7978-E7986.
[http://dx.doi.org/10.1073/pnas.1807918115 ] [PMID: 30082411]
[27]
Anderson, P.J.; Perham, R.N. The reactivity of thiol groups and the subunit structure of aldolase. Biochem. J., 1970, 117(2), 291-298.
[http://dx.doi.org/10.1042/bj1170291 ] [PMID: 5420037]
[28]
Voet, D.; Voet, J.; Pratt, C. Fundamentals of biochemistry, 3rd ed; Wiley & Sons, Inc.: Hoboken, NJ, 2008.
[29]
Martínez-Banaclocha, M.A. Cysteinet dysregulation in muscular dystrophies: a pathogenic network susceptible to therapy. Curr. Med. Chem., 2017, 24(3), 312-330.
[http://dx.doi.org/10.2174/0929867323666161129124549 ] [PMID: 27897115]
[30]
Butterfield, D.A.; Hardas, S.S.; Lange, M.L. Oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer’s disease: many pathways to neurodegeneration. J. Alzheimers Dis., 2010, 20(2), 369-393.
[http://dx.doi.org/10.3233/JAD-2010-1375 ] [PMID: 20164570]
[31]
Mailloux, R.J.; Jin, X.; Willmore, W.G. Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions. Redox Biol., 2013, 2, 123-139.
[http://dx.doi.org/10.1016/j.redox.2013.12.011 ] [PMID: 24455476]
[32]
Bulteau, A.L.; Lundberg, K.C.; Ikeda-Saito, M.; Isaya, G.; Szweda, L.I. Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion. Proc. Natl. Acad. Sci. USA, 2005, 102(17), 5987-5991.
[http://dx.doi.org/10.1073/pnas.0501519102 ] [PMID: 15840721]
[33]
Ali, M.S.; Roche, T.E.; Patel, M.S. Identification of the essential cysteine residue in the active site of bovine pyruvate dehydrogenase. J. Biol. Chem., 1993, 268(30), 22353-22356.
[PMID: 8226745]
[34]
Martínez, M.; Hernández, A.I.; Martínez, N. N-Acetylcysteine delays age-associated memory impairment in mice: role in synaptic mitochondria. Brain Res., 2000, 855(1), 100-106.
[http://dx.doi.org/10.1016/S0006-8993(99)02349-5 ] [PMID: 10650135]
[35]
Martínez Banaclocha, M. N-acetylcysteine elicited increase in complex I activity in synaptic mitochondria from aged mice: implications for treatment of Parkinson’s disease. Brain Res., 2000, 859(1), 173-175.
[http://dx.doi.org/10.1016/S0006-8993(00)02005-9 ] [PMID: 10720628]
[36]
Martínez Banaclocha, M.; Martínez, N. N-acetylcysteine elicited increase in cytochrome c oxidase activity in mice synaptic mitochondria. Brain Res., 1999, 842(1), 249-251.
[http://dx.doi.org/10.1016/S0006-8993(99)01819-3 ] [PMID: 10526120]
[37]
Banaclocha, M.M.; Hernández, A.I.; Martínez, N.; Ferrándiz, M.L. N-acetylcysteine protects against age-related increase in oxidized proteins in mouse synaptic mitochondria. Brain Res., 1997, 762(1-2), 256-258.
[http://dx.doi.org/10.1016/S0006-8993(97)00493-9 ] [PMID: 9262186]
[38]
Banaclocha, M.M. Therapeutic potential of N-acetylcysteine in age-related mitochondrial neurodegenerative diseases. Med. Hypotheses, 2001, 56(4), 472-477.
[http://dx.doi.org/10.1054/mehy.2000.1194 ] [PMID: 11339849]
[39]
Wang, S.B.; Foster, D.B.; Rucker, J.; O’Rourke, B.; Kass, D.A.; Van Eyk, J.E. Redox regulation of mitochondrial ATP synthase: implications for cardiac resynchronization therapy. Circ. Res., 2011, 109(7), 750-757.
[http://dx.doi.org/10.1161/CIRCRESAHA.111.246124 ] [PMID: 21817160]
[40]
Beer, S.M.; Taylor, E.R.; Brown, S.E.; Dahm, C.C.; Costa, N.J.; Runswick, M.J.; Murphy, M.P. Glutaredoxin 2 catalyzes the reversible oxidation and glutathionylation of mitochondrial membrane thiol proteins: implications for mitochondrial redox regulation and antioxidant DEFENSE. J. Biol. Chem., 2004, 279(46), 47939-47951.
[http://dx.doi.org/10.1074/jbc.M408011200 ] [PMID: 15347644]
[41]
Kang, P.T.; Chen, C.L.; Lin, P.; Zhang, L.; Zweier, J.L.; Chen, Y.R. Mitochondrial complex I in the post-ischemic heart: reperfusion-mediated oxidative injury and protein cysteine sulfonation. J. Mol. Cell. Cardiol., 2018, 121, 190-204.
[http://dx.doi.org/10.1016/j.yjmcc.2018.07.244 ] [PMID: 30031815]
[42]
Danielson, S.R.; Held, J.M.; Oo, M.; Riley, R.; Gibson, B.W.; Andersen, J.K. Quantitative mapping of reversible mitochondrial Complex I cysteine oxidation in a Parkinson disease mouse model. J. Biol. Chem., 2011, 286(9), 7601-7608.
[http://dx.doi.org/10.1074/jbc.M110.190108 ] [PMID: 21196577]
[43]
Guttmann, R.P. Redox regulation of cysteine-dependent enzymes. J. Anim. Sci., 2010, 88(4), 1297-1306.
[http://dx.doi.org/10.2527/jas.2009-2381 ] [PMID: 19820057]
[44]
Liesa, M.; Shirihai, O.S. Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab., 2013, 17(4), 491-506.
[http://dx.doi.org/10.1016/j.cmet.2013.03.002 ] [PMID: 23562075]
[45]
Chan, D.C. Mitochondria: dynamic organelles in disease, aging, and development. Cell, 2006, 125(7), 1241-1252.
[http://dx.doi.org/10.1016/j.cell.2006.06.010 ] [PMID: 16814712]
[46]
Shutt, T.; Geoffrion, M.; Milne, R.; McBride, H.M. The intracellular redox state is a core determinant of mitochondrial fusion. EMBO Rep., 2012, 13(10), 909-915.
[http://dx.doi.org/10.1038/embor.2012.128 ] [PMID: 22945481]
[47]
Redpath, C.J.; Bou Khalil, M.; Drozdzal, G.; Radisic, M.; McBride, H.M. Mitochondrial hyperfusion during oxidative stress is coupled to a dysregulation in calcium handling within a C2C12 cell model. PLoS One, 2013, 8(7), e69165.
[http://dx.doi.org/10.1371/journal.pone.0069165 ] [PMID: 23861961]
[48]
Mattie, S.; Riemer, J.; Wideman, J.G.; McBride, H.M. A new mitofusin topology places the redox-regulated C terminus in the mitochondrial intermembrane space. J. Cell Biol., 2018, 217(2), 507-515.
[http://dx.doi.org/10.1083/jcb.201611194 ] [PMID: 29212658]
[49]
Thaher, O.; Wolf, C.; Dey, P.N.; Pouya, A.; Wüllner, V.; Tenzer, S.; Methner, A. The thiol switch C684 in Mitofusin-2 mediates redox-induced alterations of mitochondrial shape and respiration. Neurochem. Int., 2018, 117, 167-173.
[http://dx.doi.org/10.1016/j.neuint.2017.05.009 ] [PMID: 28527631]
[50]
Flippo, K.H.; Strack, S. An emerging role for mitochondrial dynamics in schizophrenia. Schizophr. Res., 2017, 187, 26-32.
[http://dx.doi.org/10.1016/j.schres.2017.05.003 ] [PMID: 28526279]
[51]
Nakamura, T.; Lipton, S.A. Redox modulation by S-nitrosylation contributes to protein misfolding, mitochondrial dynamics, and neuronal synaptic damage in neurodegenerative diseases. Cell Death Differ., 2011, 18(9), 1478-1486.
[http://dx.doi.org/10.1038/cdd.2011.65 ] [PMID: 21597461]
[52]
Powell, S.B.; Sejnowski, T.J.; Behrens, M.M. Behavioral and neurochemical consequences of cortical oxidative stress on parvalbumin-interneuron maturation in rodent models of schizophrenia. Neuropharmacology, 2012, 62(3), 1322-1331.
[http://dx.doi.org/10.1016/j.neuropharm.2011.01.049 ] [PMID: 21315745]
[53]
Cabungcal, J.H.; Steullet, P.; Kraftsik, R.; Cuenod, M.; Do, K.Q. Early-life insults impair parvalbumin interneurons via oxidative stress: reversal by N-acetylcysteine. Biol. Psychiatry, 2013, 73(6), 574-582.
[http://dx.doi.org/10.1016/j.biopsych.2012.09.020 ] [PMID: 23140664]
[54]
Furukawa, Y.; Torres, A.S.; O’Halloran, T.V. Oxygen-induced maturation of SOD1: a key role for disulfide formation by the copper chaperone CCS. EMBO J., 2004, 23(14), 2872-2881.
[http://dx.doi.org/10.1038/sj.emboj.7600276 ] [PMID: 15215895]
[55]
Furukawa, Y.; O’Halloran, T.V. Amyotrophic lateral sclerosis mutations have the greatest destabilizing effect on the apo- and reduced form of SOD1, leading to unfolding and oxidative aggregation. J. Biol. Chem., 2005, 280(17), 17266-17274.
[http://dx.doi.org/10.1074/jbc.M500482200 ] [PMID: 15691826]
[56]
Furukawa, Y.; Kaneko, K.; Yamanaka, K.; O’Halloran, T.V.; Nukina, N. Complete loss of post-translational modifications triggers fibrillar aggregation of SOD1 in the familial form of amyotrophic lateral sclerosis. J. Biol. Chem., 2008, 283(35), 24167-24176.
[http://dx.doi.org/10.1074/jbc.M802083200 ] [PMID: 18552350]
[57]
Cozzolino, M.; Amori, I.; Pesaresi, M.G.; Ferri, A.; Nencini, M.; Carrì, M.T. Cysteine 111 affects aggregation and cytotoxicity of mutant Cu,Zn-superoxide dismutase associated with familial amyotrophic lateral sclerosis. J. Biol. Chem., 2008, 283(2), 866-874.
[http://dx.doi.org/10.1074/jbc.M705657200 ] [PMID: 18006498]
[58]
Ogawa, M.; Shidara, H.; Oka, K.; Kurosawa, M.; Nukina, N.; Furukawa, Y. Cysteine residues in Cu,Zn-superoxide dismutase are essential to toxicity in Caenorhabditis elegans model of amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun., 2015, 463(4), 1196-1202.
[http://dx.doi.org/10.1016/j.bbrc.2015.06.084 ] [PMID: 26086102]
[59]
Toichi, K.; Yamanaka, K.; Furukawa, Y. Disulfide scrambling describes the oligomer formation of superoxide dismutase (SOD1) proteins in the familial form of amyotrophic lateral sclerosis. J. Biol. Chem., 2013, 288(7), 4970-4980.
[http://dx.doi.org/10.1074/jbc.M112.414235 ] [PMID: 23264618]
[60]
Rhee, S.G. Overview on Peroxiredoxin. Mol. Cells, 2016, 39(1), 1-5.
[http://dx.doi.org/10.14348/molcells.2016.2368 ] [PMID: 26831451]
[61]
Gysin, R.; Kraftsik, R.; Sandell, J.; Bovet, P.; Chappuis, C.; Conus, P.; Deppen, P.; Preisig, M.; Ruiz, V.; Steullet, P.; Tosic, M.; Werge, T.; Cuénod, M.; Do, K.Q. Impaired glutathione synthesis in schizophrenia: convergent genetic and functional evidence. Proc. Natl. Acad. Sci. USA, 2007, 104(42), 16621-16626.
[http://dx.doi.org/10.1073/pnas.0706778104 ] [PMID: 17921251]
[62]
Tosic, M.; Ott, J.; Barral, S.; Bovet, P.; Deppen, P.; Gheorghita, F.; Matthey, M.L.; Parnas, J.; Preisig, M.; Saraga, M.; Solida, A.; Timm, S.; Wang, A.G.; Werge, T.; Cuénod, M.; Do, K.Q. Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene. Am. J. Hum. Genet., 2006, 79(3), 586-592.
[http://dx.doi.org/10.1086/507566 ] [PMID: 16909399]
[63]
Rodríguez-Santiago, B.; Brunet, A.; Sobrino, B.; Serra-Juhé, C.; Flores, R.; Armengol, L.; Vilella, E.; Gabau, E.; Guitart, M.; Guillamat, R.; Martorell, L.; Valero, J.; Gutiérrez-Zotes, A.; Labad, A.; Carracedo, A.; Estivill, X.; Pérez-Jurado, L.A. Association of common copy number variants at the glutathione S-transferase genes and rare novel genomic changes with schizophrenia. Mol. Psychiatry, 2010, 15(10), 1023-1033.
[http://dx.doi.org/10.1038/mp.2009.53 ] [PMID: 19528963]
[64]
O’Donnell, P.; Do, K.Q.; Arango, C. Oxidative/Nitrosative stress in psychiatric disorders: are we there yet? Schizophr. Bull., 2014, 40(5), 960-962.
[http://dx.doi.org/10.1093/schbul/sbu048 ] [PMID: 24714380]
[65]
Gali, R.R.; Board, P.G. Identification of an essential cysteine residue in human glutathione synthase. Biochem. J., 1997, 321(Pt 1), 207-210.
[http://dx.doi.org/10.1042/bj3210207 ] [PMID: 9003420]
[66]
Sheehan, D.; Meade, G.; Foley, V.M.; Dowd, C.A. Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem. J., 2001, 360(Pt 1), 1-16.
[http://dx.doi.org/10.1042/bj3600001 ] [PMID: 11695986]
[67]
Kenji, H.; Eiji, S.; Masaomi, I. Dysfunction of glia-neuron communication in pathophysiology of schizophrenia. Curr. Psychiatry Rev., 2005, 1, 151-163.
[http://dx.doi.org/10.2174/1573400054065569]
[68]
Lassing, I.; Schmitzberger, F.; Björnstedt, M.; Holmgren, A.; Nordlund, P.; Schutt, C.E.; Lindberg, U. Molecular and structural basis for redox regulation of β-actin. J. Mol. Biol., 2007, 370(2), 331-348.
[http://dx.doi.org/10.1016/j.jmb.2007.04.056 ] [PMID: 17521670]
[69]
McDonagh, B.; Martínez-Acedo, P.; Vázquez, J.; Padilla, C.A.; Sheehan, D.; Bárcena, J.A. Application of iTRAQ reagents to relatively quantify the reversible redox state of cysteine residues. Int. J. Proteomics, 2012, 2012, 514847.
[http://dx.doi.org/10.1155/2012/514847 ] [PMID: 22844595]
[70]
Lewis, S.A.; Cowan, N.J. Genetics, evolution, and expression of the 68,000-mol-wt neurofilament protein: isolation of a cloned cDNA probe. J. Cell Biol., 1985, 100(3), 843-850.
[http://dx.doi.org/10.1083/jcb.100.3.843 ] [PMID: 3919033]
[71]
Julien, J-P.; Côté, F.; Beaudet, L.; Sidky, M.; Flavell, D.; Grosveld, F.; Mushynski, W. Sequence and structure of the mouse gene coding for the largest neurofilament subunit. Gene, 1988, 68(2), 307-314.
[http://dx.doi.org/10.1016/0378-1119(88)90033-9 ] [PMID: 3220257]
[72]
Takeda, S.; Okabe, S.; Funakoshi, T.; Hirokawa, N. Differential dynamics of neurofilament-H protein and neurofilament-L protein in neurons. J. Cell Biol., 1994, 127(1), 173-185.
[http://dx.doi.org/10.1083/jcb.127.1.173 ] [PMID: 7929561]
[73]
Purcell, S.M.; Wray, N.R.; Stone, J.L.; Visscher, P.M.; O’Donovan, M.C.; Sullivan, P.F.; Sklar, P. International Schizophrenia Consortium. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature, 2009, 460(7256), 748-752.
[http://dx.doi.org/10.1038/nature08185 ] [PMID: 19571811]
[74]
Callicott, J.H.; Straub, R.E.; Pezawas, L.; Egan, M.F.; Mattay, V.S.; Hariri, A.R.; Verchinski, B.A.; Meyer-Lindenberg, A.; Balkissoon, R.; Kolachana, B.; Goldberg, T.E.; Weinberger, D.R. Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc. Natl. Acad. Sci. USA, 2005, 102(24), 8627-8632.
[http://dx.doi.org/10.1073/pnas.0500515102 ] [PMID: 15939883]
[75]
Takahashi, T.; Suzuki, M.; Tsunoda, M.; Maeno, N.; Kawasaki, Y.; Zhou, S.Y.; Hagino, H.; Niu, L.; Tsuneki, H.; Kobayashi, S.; Sasaoka, T.; Seto, H.; Kurachi, M.; Ozaki, N. The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain morphology in schizophrenia. Psychiatry Res., 2009, 172(2), 128-135.
[http://dx.doi.org/10.1016/j.pscychresns.2009.01.005 ] [PMID: 19304459]
[76]
Takahashi, T.; Nakamura, M.; Nakamura, Y.; Aleksic, B.; Kido, M.; Sasabayashi, D.; Takayanagi, Y.; Furuichi, A.; Nishikawa, Y.; Noguchi, K.; Ozaki, N.; Suzuki, M. The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain neurodevelopmental markers in schizophrenia and healthy subjects. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2015, 56, 11-17.
[http://dx.doi.org/10.1016/j.pnpbp.2014.07.005 ] [PMID: 25092219]
[77]
Li, Y.; Liu, B.; Hou, B.; Qin, W.; Wang, D.; Yu, C.; Jiang, T. Less efficient information transfer in Cys-allele carriers of DISC1: a brain network study based on diffusion MRI. Cereb. Cortex, 2013, 23(7), 1715-1723.
[http://dx.doi.org/10.1093/cercor/bhs167 ] [PMID: 22693340]
[78]
Salim, S. Oxidative stress and the central nervous system. J. Pharmacol. Exp. Ther., 2017, 360(1), 201-205.
[http://dx.doi.org/10.1124/jpet.116.237503 ] [PMID: 27754930]
[79]
Viedma-Poyatos, Á.; de Pablo, Y.; Pekny, M.; Pérez-Sala, D. The cysteine residue of glial fibrillary acidic protein is a critical target for lipoxidation and required for efficient network organization. Free Radic. Biol. Med., 2018, 120, 380-394.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.007 ] [PMID: 29635011]
[80]
Gellert, M.; Venz, S.; Mitlöhner, J.; Cott, C.; Hanschmann, E.M.; Lillig, C.H. Identification of a dithiol-disulfide switch in collapsin response mediator protein 2 (CRMP2) that is toggled in a model of neuronal differentiation. J. Biol. Chem., 2013, 288(49), 35117-35125.
[http://dx.doi.org/10.1074/jbc.M113.521443 ] [PMID: 24133216]
[81]
Freudenberg, F.; Alttoa, A.; Reif, A. Neuronal nitric oxide synthase (NOS1) and its adaptor, NOS1AP, as a genetic risk factors for psychiatric disorders. Genes Brain Behav., 2015, 14(1), 46-63.
[http://dx.doi.org/10.1111/gbb.12193 ] [PMID: 25612209]
[82]
Martásek, P.; Miller, R.T.; Liu, Q.; Roman, L.J.; Salerno, J.C.; Migita, C.T.; Raman, C.S.; Gross, S.S.; Ikeda-Saito, M.; Masters, B.S. The C331A mutant of neuronal nitric-oxide synthase is defective in arginine binding. J. Biol. Chem., 1998, 273(52), 34799-34805.
[http://dx.doi.org/10.1074/jbc.273.52.34799 ] [PMID: 9857005]
[83]
Arami, K.M.; Jameie, B.; Moosavi, S.A. Neuronal nitric oxide synthase; IntechOpen, 2017.
[http://dx.doi.org/10.5772/67494]
[84]
Greco, T.M.; Hodara, R.; Parastatidis, I.; Heijnen, H.F.; Dennehy, M.K.; Liebler, D.C.; Ischiropoulos, H. Identification of S-nitrosylation motifs by site-specific mapping of the S-nitrosocysteine proteome in human vascular smooth muscle cells. Proc. Natl. Acad. Sci. USA, 2006, 103(19), 7420-7425.
[http://dx.doi.org/10.1073/pnas.0600729103 ] [PMID: 16648260]
[85]
Hao, G.; Derakhshan, B.; Shi, L.; Campagne, F.; Gross, S.S. SNOSID, a proteomic method for identification of cysteine S-nitrosylation sites in complex protein mixtures. Proc. Natl. Acad. Sci. USA, 2006, 103(4), 1012-1017.
[http://dx.doi.org/10.1073/pnas.0508412103 ] [PMID: 16418269]
[86]
Paulsen, C.E.; Carroll, K.S. Cysteine-mediated redox signaling: chemistry, biology, and tools for discovery. Chem. Rev., 2013, 113(7), 4633-4679.
[http://dx.doi.org/10.1021/cr300163e ] [PMID: 23514336]
[87]
Migaud, M.; Charlesworth, P.; Dempster, M.; Webster, L.C.; Watabe, A.M.; Makhinson, M.; He, Y.; Ramsay, M.F.; Morris, R.G.; Morrison, J.H.; O’Dell, T.J.; Grant, S.G. Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature, 1998, 396(6710), 433-439.
[http://dx.doi.org/10.1038/24790 ] [PMID: 9853749]
[88]
Jemth, P.; Gianni, S. PDZ domains: folding and binding. Biochemistry, 2007, 46(30), 8701-8708.
[http://dx.doi.org/10.1021/bi7008618 ] [PMID: 17620015]
[89]
Carrel, D.; Hernandez, K.; Kwon, M.; Mau, C.; Trivedi, M.P.; Brzustowicz, L.M.; Firestein, B.L. Nitric oxide synthase 1 adaptor protein, a protein implicated in schizophrenia, controls radial migration of cortical neurons. Biol. Psychiatry, 2015, 77(11), 969-978.
[http://dx.doi.org/10.1016/j.biopsych.2014.10.016 ] [PMID: 25542305]
[90]
Ho, G.P.; Selvakumar, B.; Mukai, J.; Hester, L.D.; Wang, Y.; Gogos, J.A.; Snyder, S.H. S-nitrosylation and S-palmitoylation reciprocally regulate synaptic targeting of PSD-95. Neuron, 2011, 71(1), 131-141.
[http://dx.doi.org/10.1016/j.neuron.2011.05.033 ] [PMID: 21745643]
[91]
Cheah, J.H.; Kim, S.F.; Hester, L.D.; Clancy, K.W.; Patterson, S.E., III; Papadopoulos, V.; Snyder, S.H. NMDA receptor-nitric oxide transmission mediates neuronal iron homeostasis via the GTPase Dexras1. Neuron, 2006, 51(4), 431-440.
[http://dx.doi.org/10.1016/j.neuron.2006.07.011 ] [PMID: 16908409]
[92]
Carrel, D.; Du, Y.; Komlos, D.; Hadzimichalis, N.M.; Kwon, M.; Wang, B.; Brzustowicz, L.M.; Firestein, B.L. NOS1AP regulates dendrite patterning of hippocampal neurons through a carboxypeptidase E-mediated pathway. J. Neurosci., 2009, 29(25), 8248-8258.
[http://dx.doi.org/10.1523/JNEUROSCI.5287-08.2009 ] [PMID: 19553464]
[93]
Hernandez, K.; Swiatkowski, P.; Patel, M.V.; Liang, C.; Dudzinski, N.R.; Brzustowicz, L.M.; Firestein, B.L. Overexpression of isoforms of nitric oxide synthase 1 adaptor protein, encoded by a risk gene for schizophrenia, alters actin dynamics and synaptic function. Front. Cell. Neurosci., 2016, 10, 6.
[http://dx.doi.org/10.3389/fncel.2016.00006 ] [PMID: 26869880]
[94]
Detera-Wadleigh, S.D.; McMahon, F.J. G72/G30 in schizophrenia and bipolar disorder: review and meta-analysis. Biol. Psychiatry, 2006, 60(2), 106-114.
[http://dx.doi.org/10.1016/j.biopsych.2006.01.019 ] [PMID: 16581030]
[95]
Pósfai, B.; Cserép, C.; Hegedüs, P.; Szabadits, E.; Otte, D.M.; Zimmer, A.; Watanabe, M.; Freund, T.F.; Nyiri, G. Synaptic and cellular changes induced by the schizophrenia susceptibility gene G72 are rescued by N-acetylcysteine treatment. Transl. Psychiatry, 2016, 6(5), e807.
[http://dx.doi.org/10.1038/tp.2016.74 ] [PMID: 27163208]
[96]
Otte, D.M.; Sommersberg, B.; Kudin, A.; Guerrero, C.; Albayram, O.; Filiou, M.D.; Frisch, P.; Yilmaz, O.; Drews, E.; Turck, C.W.; Bilkei-Gorzó, A.; Kunz, W.S.; Beck, H.; Zimmer, A. N-acetyl cysteine treatment rescues cognitive deficits induced by mitochondrial dysfunction in G72/G30 transgenic mice. Neuropsychopharmacology, 2011, 36(11), 2233-2243.
[http://dx.doi.org/10.1038/npp.2011.109 ] [PMID: 21716263]
[97]
Otte, D.M.; Raskó, T.; Wang, M.; Dreiseidler, M.; Drews, E.; Schrage, H.; Wojtalla, A.; Höhfeld, J.; Wanker, E.; Zimmer, A. Identification of the mitochondrial MSRB2 as a binding partner of LG72. Cell. Mol. Neurobiol., 2014, 34(8), 1123-1130.
[http://dx.doi.org/10.1007/s10571-014-0087-0 ] [PMID: 25078755]
[98]
Arinami, T.; Itokawa, M.; Enguchi, H.; Tagaya, H.; Yano, S.; Shimizu, H.; Hamaguchi, H.; Toru, M. Association of dopamine D2 receptor molecular variant with schizophrenia. Lancet, 1994, 343(8899), 703-704.
[http://dx.doi.org/10.1016/S0140-6736(94)91581-4 ] [PMID: 7907680]
[99]
Kaneshima, M.; Higa, T.; Nakamoto, H.; Nagamine, M. An association study between the Cys311 variant of dopamine D2 receptor gene and schizophrenia in the Okinawan population. Psychiatry Clin. Neurosci., 1997, 51(6), 379-381.
[http://dx.doi.org/10.1111/j.1440-1819.1997.tb02603.x ] [PMID: 9472122]
[100]
Tallerico, T.; Ulpian, C.; Liu, I.S. Dopamine D2 receptor promoter polymorphism: no association with schizophrenia. Psychiatry Res., 1999, 85(2), 215-219.
[http://dx.doi.org/10.1016/S0165-1781(98)00125-5 ] [PMID: 10220012]
[101]
Serretti, A.; Lilli, R.; Lorenzi, C.; Smeraldi, E. Further evidence supporting the association between the dopamine receptor D2 Ser/Cys311 variant and disorganized symptomatology of schizophrenia. Schizophr. Res., 2000, 43(2-3), 161-162.
[PMID: 11001590]
[102]
Göthert, M.; Propping, P.; Bönisch, H.; Brüss, M.; Nöthen, M.M. Genetic variation in human 5-HT receptors: potential pathogenetic and pharmacological role. Ann. N. Y. Acad. Sci., 1998, 861, 26-30.
[http://dx.doi.org/10.1111/j.1749-6632.1998.tb10169.x ] [PMID: 9928235]
[103]
Howes, O.; McCutcheon, R.; Stone, J. Glutamate and dopamine in schizophrenia: an update for the 21st century. J. Psychopharmacol. (Oxford), 2015, 29(2), 97-115.
[http://dx.doi.org/10.1177/0269881114563634 ] [PMID: 25586400]
[104]
McBean, G.J. Cerebral cystine uptake: a tale of two transporters. Trends Pharmacol. Sci., 2002, 23(7), 299-302.
[http://dx.doi.org/10.1016/S0165-6147(02)02060-6 ] [PMID: 12119142]
[105]
Dringen, R.; Pfeiffer, B.; Hamprecht, B. Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. J. Neurosci., 1999, 19(2), 562-569.
[http://dx.doi.org/10.1523/JNEUROSCI.19-02-00562.1999 ] [PMID: 9880576]
[106]
Conrad, M.; Sato, H. The oxidative stress-inducible cystine/glutamate antiporter, system x (c) (-): cystine supplier and beyond. Amino Acids, 2012, 42(1), 231-246.
[http://dx.doi.org/10.1007/s00726-011-0867-5 ] [PMID: 21409388]
[107]
Sagara, J.I.; Miura, K.; Bannai, S. Maintenance of neuronal glutathione by glial cells. J. Neurochem., 1993, 61(5), 1672-1676.
[http://dx.doi.org/10.1111/j.1471-4159.1993.tb09802.x ] [PMID: 8228986]
[108]
Banjac, A.; Perisic, T.; Sato, H.; Seiler, A.; Bannai, S.; Weiss, N.; Kölle, P.; Tschoep, K.; Issels, R.D.; Daniel, P.T.; Conrad, M.; Bornkamm, G.W. The cystine/cysteine cycle: a redox cycle regulating susceptibility versus resistance to cell death. Oncogene, 2008, 27(11), 1618-1628.
[http://dx.doi.org/10.1038/sj.onc.1210796 ] [PMID: 17828297]
[109]
Lewerenz, J.; Hewett, S.J.; Huang, Y.; Lambros, M.; Gout, P.W.; Kalivas, P.W.; Massie, A.; Smolders, I.; Methner, A.; Pergande, M.; Smith, S.B.; Ganapathy, V.; Maher, P. The cystine/glutamate antiporter system x(c)(-) in health and disease: from molecular mechanisms to novel therapeutic opportunities. Antioxid. Redox Signal., 2013, 18(5), 522-555.
[http://dx.doi.org/10.1089/ars.2011.4391 ] [PMID: 22667998]
[110]
Klauser, P.; Xin, L.; Fournier, M.; Griffa, A.; Cleusix, M.; Jenni, R.; Cuenod, M.; Gruetter, R.; Hagmann, P.; Conus, P.; Baumann, P.S.; Do, K.Q. N-acetylcysteine add-on treatment leads to an improvement of fornix white matter integrity in early psychosis: a double-blind randomized placebo-controlled trial. Transl. Psychiatry, 2018, 8(1), 220.
[http://dx.doi.org/10.1038/s41398-018-0266-8 ] [PMID: 30315150]
[111]
Gleixner, A.M.; Hutchison, D.F.; Sannino, S.; Bhatia, T.N.; Leak, L.C.; Flaherty, P.T.; Wipf, P.; Brodsky, J.L.; Leak, R.K. N-acetyl-L-cysteine protects astrocytes against proteotoxicity without recourse to glutathione. Mol. Pharmacol., 2017, 92(5), 564-575.
[http://dx.doi.org/10.1124/mol.117.109926 ] [PMID: 28830914]
[112]
Davidson, M. Risk of cardiovascular disease and sudden death in schizophrenia. J. Clin. Psychiatry, 2002, 63(Suppl. 9), 5-11.
[PMID: 12088174]
[113]
Ringen, P.A.; Engh, J.A.; Birkenaes, A.B.; Dieset, I.; Andreassen, O.A. Increased mortality in schizophrenia due to cardiovascular disease - a non-systematic review of epidemiology, possible causes, and interventions. Front. Psychiatry, 2014, 5, 137.
[http://dx.doi.org/10.3389/fpsyt.2014.00137 ] [PMID: 25309466]
[114]
Talasaz, A.H.; Khalili, H.; Fahimi, F. Potential role of N-acetylcisteine in cardiovascular disorders. Therapy, 2011, 8, 237-245.
[http://dx.doi.org/10.2217/thy.11.12]
[115]
Ozcelik, D.; Uzun, H.; Nazıroglu, M. N-acetylcysteine attenuates copper overload-induced oxidative injury in brain of rat. Biol. Trace Elem. Res., 2012, 147(1-3), 292-298.
[http://dx.doi.org/10.1007/s12011-012-9320-1 ] [PMID: 22246790]
[116]
Tarantino, G.; Porcu, C.; Arciello, M.; Andreozzi, P.; Balsano, C. Prediction of carotid intima-media thickness in obese patients with low prevalence of comorbidities by serum copper bioavailability. J. Gastroenterol. Hepatol., 2018, 33(8), 1511-1517.
[http://dx.doi.org/10.1111/jgh.14104 ] [PMID: 29405466]
[117]
Bowman, M.B.; Lewis, M.S. The copper hypothesis of schizophrenia: a review. Neurosci. Biobehav. Rev., 1982, 6(3), 321-328.
[http://dx.doi.org/10.1016/0149-7634(82)90044-6 ] [PMID: 7177508]