BibTex RIS Kaynak Göster

The involvement of Akt and GSK-3: Two pathways, two pathology

Yıl 2014, Cilt: 4 Sayı: 1, 51 - 57, 25.04.2014

Ceren Şahin Gökhan Ünal Feyza Arıcıoğlu

Öz

Today a growing body of evidence has directed much attention to the hyperactivation of glycogen synthase kinase-3 (GSK-3) in several psychiatric disorders including schizophrenia and mood disorders. Regulatory mechanisms of GSK-3 activation have become important issues since GSK-3, a member of serine/threonine kinase family, is identified to have numerous roles in intracellular functions by its effect on regulation of at least fifty protein substrates. Among these, particularly the inhibitory control of GSK-3 by Akt is considered as one of the most intriguing mechanisms in psychiatric manner. Hence, in schizophrenia and depression, disruption of Akt-mediated regulation of GSK-3 via two distinct pathways is resulted in hyperactivated GSK-3. In the present study, alterations of two Akt-mediated regulatory mechanisms of GSK-3; phosphoinositide-3 kinase (PI3K) and ß-arrestin complex mediated pathways are reviewed in depression and schizophrenia respectively, and how these alterations reflect GSK-3 activity and consequently contribute to the development of these conditions. Finally the importance of regulatory mechanisms on GSK-3 is highlighted through the aspect of Akt-GSK-3 engagement by possibly bringing novel aspects to the treatments of these disorders.

Key words: Akt, GSK-3, PI3K, ß-arrestin, depression, schizophrenia

Anahtar Kelimeler

Akt GSK-3 PI3K β-arrestin depression schizophrenia

Kaynakça

  • Embi N, Rylatt DB, Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem. 1980; 107(2): 519–527.
  • Woodgett JR. Molecular cloning and expression of glycogen synthase kinase-3/factor A. Embo J. 1990; 9(8): 2431-2438.
  • Doble BW, Woodgett JR. GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci. 2003; 116(7): 1175-1186.
  • Kim M, Datta A, Brakeman P, Yu W, Mostov KE. Polarity proteins PAR6 and aPKC regulate cell death through GSK-3beta in 3D epithelial morphogenesis. J Cell Sci. 2007; 120(14): 2309-2317.
  • Cole AR. GSK-3 as a sensor determining cell fate in the brain. Front Mol Neurosci. 2012; 5:4.
  • Kim WY, Snider WD. Functions of GSK-3 signaling in development of the nervous system. Front Mol Neurosci. 2011; 4: 44.
  • Nayak G, Cooper GM. P53 is a major component of the transcriptional and apoptotic program regulated by PI3-kinase/Akt/GSK3 signaling. Cell Death Dis. 2012; 3(10): 400.
  • Hongo H, Kihara T, Kume T, Izumi Y, Niidome T, Sugimoto H, Akaike A. Glycogen synthase kinase-3beta activation mediates rotenone-induced cytotoxicity with the involvement of microtubule destabilization. Biochem Biophys Res Commun. 2012; 426(1): 94-99.
  • Manceur AP, Tseng M, Holowacz T, Witterick I, Weksberg R, McCurdy RD, Warsh JJ, Audet J. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors. Exp Cell Res. 2011; 317(15): 2086-2098.
  • Cole AR. Glycogen synthase kinase 3 substrates in mood disorders and schizophrenia. FEBS J. 2013; 280(21): 5213–5227.
  • Jope RS, Roh MS. Glycogen Synthase Kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions. Curr Drug Targets. 2006; 7(11): 1421–1434.
  • Meijer L, Flajolet M, Greengard P. Pharmacological inhibitors of glycogen synthase kinase 3. TRENDS in Pharmacological Sciences. 2004; 25(9): 471-480.
  • Beaulieu JM. A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health. J Psychiatry Neurosci. 2012; 37(1): 7-16.
  • Beaulieu JM, Gainetdinov RR, Caron MG. Akt/GSK3 Signaling in the Action of Psychotropic Drugs. Annu Rev Pharmacol Toxicol. 2009; 49: 327-3
  • Emamian ES. AKT/GSK3 signaling pathway and schizophrenia. Front Mol Neurosci. 2012; 5(33): 1-12.
  • Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995; 378(6559): 785–789.
  • Fang X, Yu SX, Lu Y, Bast Jr RC, Woodgett JR, Mills GB. Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. Proc Natl Acad Sci USA. 2000; 97(22): 11960–11965.
  • Hsiung SC, Adlersberg M, Arango V, Mann JJ, Tamir H, Liu KP. Attenuated 5-HT1A receptor signaling in brains of suicide victims: involvement of adenylyl cyclase, phosphatidylinositol 3-kinase, Akt and mitogen-activated protein kinase. J Neurochem. 2003; 87(1): 182–194.
  • Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG. An Akt/β-Arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell. 2005; 122(2): 261–73.
  • Matrisciano F, Bonaccorso S, Ricciardi A, Scaccianoce S, Panaccione I, Wang L, Ruberto A, Tatarelli R, Nicoletti F, Girardi P, Shelton RC. Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine. J Psychiatr Res. 2009; 43(3): 247–254.
  • Sen S, Duman R, Sanacora G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry. 2008; 64(6): 527–532.
  • Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry. 2003; 54(1): 70–75.
  • Johnson-Farley NN, Traykina T, Cowen DS. Cumulative activation of akt and consequent inhibition of glycogen synthase kines-2 by brain-derived neurotrophic factor and insulin-like growth factor-1 in cultured hippocampal neurons. J Pharmacol Exp Ther. 2006; 316(6): 1062-1069.
  • Kaidanovich-Beilin O, Milman A, Weizman A, Pick CG, Eldar-Finkelman H. Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on β-catenin in mouse hippocampus. Biol Psychiat. 2004; 55(8): 781–784.
  • O’Brien WT, Harper AD, Jove F, Woodgett JR, Maretto S, Piccolo S, Klein PS. Glycogen synthase kinase-3β haploinsufficiency mimics the behavioral and molecular effects of lithium. J Neurosci. 2004; 24(30): 6791–6798.
  • Gould TD, Einat H, Bhat R, Manji HK. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol. 2004; 7(4): 387–390.
  • Li X, Zhu W, Roh MS, Friedman AB, Rosborough K, Jope RS. In vivo regulation of glycogen synthase kinase-3 beta (GSK3beta) by serotonergic activity in mouse brain. Neuropsychopharmacology. 2004; 29(8): 1426-1431.
  • Sutton LP, Rushlow WJ. The effects of neuropsychiatric drugs on glycogen synthase kinase-3 signaling. Neuroscience. 2011; 199: 1161
  • Liu R, Dang W, Jianting M, Su C, Wang H, Chen Y, Tan Q. Citalopram alleviates chronic stress induced depression-like behaviors in rats by activating GSK3β signaling in dorsal hippocampus. Brain Res. 2012; 1467: 10-17.
  • Chen YC, Tan QR, Dang W, Wang HN, Zhang RB, Li ZY, Lin H, Liu R. The effect of citalopram on chronic stress-induced depressive-like behavior in rats through GSK3β/β-catenin activation in the medial prefrontal cortex. Brain Res Bull. 2012; 88(4): 338-344.
  • Beaulieu JM, Sotnikova TD, Yao WD, Kpckeritz L, Woodgett JR, Gainetdinov RR, Caron MG. Lithium antagonizes dopaminedependent behaviors mediated by Akt/glycogen synthase kinase 3 signaling cascade. Proc Natl Acad Sci. 2004; 101(14): 5099–5104.
  • Skinbjerg M, Ariano MA, Thorsell A, Heilig M, Halldin C, Innis RB, Sibley DR. Arrestin3 mediates D2 dopamine receptor internalization. Synapse. 2009; 63: 621–624.
  • Klewe IV, Nielsen SM, Tarpo L, Urizar E, Dipace C, Javitch JA, Gether U, Egebjerg J, Christensen KV. Recruitmentof β-arrestin2 to the dopamineD2receptor: insights into anti-psychoticand antiparkinsonian drug receptor signaling. Neuropharmacology. 2008; 54: 1215–1222.
  • Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet. 2004; 36(2): 131-137.
  • Ksiezak-Reding Z, Riggio H, Haroutunian SV, Pasinetti GM. Insulin receptor deficits in schizophrenia and incellular and animal models of insulin receptor dysfunction. Schizophr Res. 2006; 84: 1-14.
  • Thiselton DL, Vladimirov VI, Kuo PH, McClay J, Wormley B, Fanous A, O’Neill FA, Walsh D, Van den Oord EJ, Kendler KS, Riley BP. AKT1 is associated with schizophrenia across multiple symptom dimensions in the Irish study of high density schizophrenia families. Biol. Psychiatry. 2008; 63: 449–457.
  • Park SW, Phuong VT, Lee CH, Lee JG, Seo MK, Cho HY Fang ZH, Lee BJ, Kim YH. Effects of antipsychotic drugs on BDNF, GSK-3β, and β-catenin expression in rats subjected to immobilization stress. Neurosci Res. 2011;71(4):335-340.
  • Basta-Kaim A, Budziszewska B, Jagła G, Nowak W, Kubera M, Lasoń W. Inhibitory effect of antipsychotic drugs on the Con A- and LPS-induced proliferative activity of mousesplenocytes: a possible mechanism of action. J Physiol Pharmacol. 2006; 57(2): 247-264.
  • Li X, Rosborough KM, Friedman AB, Zhu W, Roth KA. Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics. Int J Neuropsychopharmacol. 2007; 10(1): 7-19.
  • Lee JG, Cho HY, Park SW, Seo MK, Kim YH. Effects of olanzapine on brain-derived neurotrophic factor gene promoter activity in SH-SY5Y neuroblastoma cells. Prog Neuropsychopharmacol Biol Psychiatry. 2010; 34(6):1001-1006.
  • Valvezan AJ, Klein PS. GSK-3 and Wnt signaling in neurogenesis and bipolar disorder. Front Mol Neurosci. 2012; 30; 5:1.

Akt-GSK-3 ilişkisi: İki ayrı yolak iki ayrı hastalık

Yıl 2014, Cilt: 4 Sayı: 1, 51 - 57, 25.04.2014

Ceren Şahin Gökhan Ünal Feyza Arıcıoğlu

Öz

Günümüzde şizofreni ve duygu durum bozukluklarını kapsayan birçok psikiyatrik hastalıkta glikojen sentaz kinaz-3 (GSK-3) hiperaktivitesine işaret edilmektedir. Serin / treonin kinaz ailesinin bir üyesi olan GSK-3’ün ellinin üzerinde proteinin regülasyonunda rol alarak hücre içi fonksiyonlarda yaygın görevlerinin olması, GSK-3 aktivitesi üzerine etkili hücre içi düzenleyici mekanizmaların önemini gündeme getirmiştir. İlgili mekanizmalardan özellikle Akt’ın GSK-3 aktivitesi üzerindeki inhibe edici rolü, psikiyatrik hastalıklar açısından oldukça dikkat çekici bir mekanizma olarak karşımıza çıkmaktadır. Nitekim Akt’ın iki farklı yolak üzerinden GSK-3 aktivitesini düzenlemesi, depresyon ve şizofreni tablosunda bozulan Akt aktivitesi sonucu GSK-3 hiperaktivitesine neden olmaktadır. Burada GSK-3 aktivitesinin düzenlenmesinde rol oynayan fosfoinozitid-3 kinaz (PI3K) ve ß-arrestin kompleksi üzerinden işleyen Akt aracılı iki farklı yolağın sırasıyla depresyon ve şizforeni tablolarında gösterdikleri değişim ile bu değişimin GSK-3 aktivitesine olan yansımasına değinilerek, Akt-GSK-3 ilişkisi bakış açısıyla GSK-3 aktivitesi üzerindeki düzenleyici mekanizmaların bu hastalıkların tedavisine getirebileceği olası boyutların önemine dikkat çekilmesi amaçlanmıştır.

Anahtar Kelimeler : Akt, GSK-3, PI3K, ß-arrestin, depresyon, şizofreni

Anahtar Kelimeler

Akt GSK-3 PI3K β-arrestin depresyon şizofreni

Kaynakça

  • Embi N, Rylatt DB, Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur J Biochem. 1980; 107(2): 519–527.
  • Woodgett JR. Molecular cloning and expression of glycogen synthase kinase-3/factor A. Embo J. 1990; 9(8): 2431-2438.
  • Doble BW, Woodgett JR. GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci. 2003; 116(7): 1175-1186.
  • Kim M, Datta A, Brakeman P, Yu W, Mostov KE. Polarity proteins PAR6 and aPKC regulate cell death through GSK-3beta in 3D epithelial morphogenesis. J Cell Sci. 2007; 120(14): 2309-2317.
  • Cole AR. GSK-3 as a sensor determining cell fate in the brain. Front Mol Neurosci. 2012; 5:4.
  • Kim WY, Snider WD. Functions of GSK-3 signaling in development of the nervous system. Front Mol Neurosci. 2011; 4: 44.
  • Nayak G, Cooper GM. P53 is a major component of the transcriptional and apoptotic program regulated by PI3-kinase/Akt/GSK3 signaling. Cell Death Dis. 2012; 3(10): 400.
  • Hongo H, Kihara T, Kume T, Izumi Y, Niidome T, Sugimoto H, Akaike A. Glycogen synthase kinase-3beta activation mediates rotenone-induced cytotoxicity with the involvement of microtubule destabilization. Biochem Biophys Res Commun. 2012; 426(1): 94-99.
  • Manceur AP, Tseng M, Holowacz T, Witterick I, Weksberg R, McCurdy RD, Warsh JJ, Audet J. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors. Exp Cell Res. 2011; 317(15): 2086-2098.
  • Cole AR. Glycogen synthase kinase 3 substrates in mood disorders and schizophrenia. FEBS J. 2013; 280(21): 5213–5227.
  • Jope RS, Roh MS. Glycogen Synthase Kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions. Curr Drug Targets. 2006; 7(11): 1421–1434.
  • Meijer L, Flajolet M, Greengard P. Pharmacological inhibitors of glycogen synthase kinase 3. TRENDS in Pharmacological Sciences. 2004; 25(9): 471-480.
  • Beaulieu JM. A role for Akt and glycogen synthase kinase-3 as integrators of dopamine and serotonin neurotransmission in mental health. J Psychiatry Neurosci. 2012; 37(1): 7-16.
  • Beaulieu JM, Gainetdinov RR, Caron MG. Akt/GSK3 Signaling in the Action of Psychotropic Drugs. Annu Rev Pharmacol Toxicol. 2009; 49: 327-3
  • Emamian ES. AKT/GSK3 signaling pathway and schizophrenia. Front Mol Neurosci. 2012; 5(33): 1-12.
  • Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 1995; 378(6559): 785–789.
  • Fang X, Yu SX, Lu Y, Bast Jr RC, Woodgett JR, Mills GB. Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. Proc Natl Acad Sci USA. 2000; 97(22): 11960–11965.
  • Hsiung SC, Adlersberg M, Arango V, Mann JJ, Tamir H, Liu KP. Attenuated 5-HT1A receptor signaling in brains of suicide victims: involvement of adenylyl cyclase, phosphatidylinositol 3-kinase, Akt and mitogen-activated protein kinase. J Neurochem. 2003; 87(1): 182–194.
  • Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG. An Akt/β-Arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell. 2005; 122(2): 261–73.
  • Matrisciano F, Bonaccorso S, Ricciardi A, Scaccianoce S, Panaccione I, Wang L, Ruberto A, Tatarelli R, Nicoletti F, Girardi P, Shelton RC. Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine. J Psychiatr Res. 2009; 43(3): 247–254.
  • Sen S, Duman R, Sanacora G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry. 2008; 64(6): 527–532.
  • Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S, Iyo M. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry. 2003; 54(1): 70–75.
  • Johnson-Farley NN, Traykina T, Cowen DS. Cumulative activation of akt and consequent inhibition of glycogen synthase kines-2 by brain-derived neurotrophic factor and insulin-like growth factor-1 in cultured hippocampal neurons. J Pharmacol Exp Ther. 2006; 316(6): 1062-1069.
  • Kaidanovich-Beilin O, Milman A, Weizman A, Pick CG, Eldar-Finkelman H. Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on β-catenin in mouse hippocampus. Biol Psychiat. 2004; 55(8): 781–784.
  • O’Brien WT, Harper AD, Jove F, Woodgett JR, Maretto S, Piccolo S, Klein PS. Glycogen synthase kinase-3β haploinsufficiency mimics the behavioral and molecular effects of lithium. J Neurosci. 2004; 24(30): 6791–6798.
  • Gould TD, Einat H, Bhat R, Manji HK. AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol. 2004; 7(4): 387–390.
  • Li X, Zhu W, Roh MS, Friedman AB, Rosborough K, Jope RS. In vivo regulation of glycogen synthase kinase-3 beta (GSK3beta) by serotonergic activity in mouse brain. Neuropsychopharmacology. 2004; 29(8): 1426-1431.
  • Sutton LP, Rushlow WJ. The effects of neuropsychiatric drugs on glycogen synthase kinase-3 signaling. Neuroscience. 2011; 199: 1161
  • Liu R, Dang W, Jianting M, Su C, Wang H, Chen Y, Tan Q. Citalopram alleviates chronic stress induced depression-like behaviors in rats by activating GSK3β signaling in dorsal hippocampus. Brain Res. 2012; 1467: 10-17.
  • Chen YC, Tan QR, Dang W, Wang HN, Zhang RB, Li ZY, Lin H, Liu R. The effect of citalopram on chronic stress-induced depressive-like behavior in rats through GSK3β/β-catenin activation in the medial prefrontal cortex. Brain Res Bull. 2012; 88(4): 338-344.
  • Beaulieu JM, Sotnikova TD, Yao WD, Kpckeritz L, Woodgett JR, Gainetdinov RR, Caron MG. Lithium antagonizes dopaminedependent behaviors mediated by Akt/glycogen synthase kinase 3 signaling cascade. Proc Natl Acad Sci. 2004; 101(14): 5099–5104.
  • Skinbjerg M, Ariano MA, Thorsell A, Heilig M, Halldin C, Innis RB, Sibley DR. Arrestin3 mediates D2 dopamine receptor internalization. Synapse. 2009; 63: 621–624.
  • Klewe IV, Nielsen SM, Tarpo L, Urizar E, Dipace C, Javitch JA, Gether U, Egebjerg J, Christensen KV. Recruitmentof β-arrestin2 to the dopamineD2receptor: insights into anti-psychoticand antiparkinsonian drug receptor signaling. Neuropharmacology. 2008; 54: 1215–1222.
  • Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet. 2004; 36(2): 131-137.
  • Ksiezak-Reding Z, Riggio H, Haroutunian SV, Pasinetti GM. Insulin receptor deficits in schizophrenia and incellular and animal models of insulin receptor dysfunction. Schizophr Res. 2006; 84: 1-14.
  • Thiselton DL, Vladimirov VI, Kuo PH, McClay J, Wormley B, Fanous A, O’Neill FA, Walsh D, Van den Oord EJ, Kendler KS, Riley BP. AKT1 is associated with schizophrenia across multiple symptom dimensions in the Irish study of high density schizophrenia families. Biol. Psychiatry. 2008; 63: 449–457.
  • Park SW, Phuong VT, Lee CH, Lee JG, Seo MK, Cho HY Fang ZH, Lee BJ, Kim YH. Effects of antipsychotic drugs on BDNF, GSK-3β, and β-catenin expression in rats subjected to immobilization stress. Neurosci Res. 2011;71(4):335-340.
  • Basta-Kaim A, Budziszewska B, Jagła G, Nowak W, Kubera M, Lasoń W. Inhibitory effect of antipsychotic drugs on the Con A- and LPS-induced proliferative activity of mousesplenocytes: a possible mechanism of action. J Physiol Pharmacol. 2006; 57(2): 247-264.
  • Li X, Rosborough KM, Friedman AB, Zhu W, Roth KA. Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics. Int J Neuropsychopharmacol. 2007; 10(1): 7-19.
  • Lee JG, Cho HY, Park SW, Seo MK, Kim YH. Effects of olanzapine on brain-derived neurotrophic factor gene promoter activity in SH-SY5Y neuroblastoma cells. Prog Neuropsychopharmacol Biol Psychiatry. 2010; 34(6):1001-1006.
  • Valvezan AJ, Klein PS. GSK-3 and Wnt signaling in neurogenesis and bipolar disorder. Front Mol Neurosci. 2012; 30; 5:1.
Toplam 41 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Articles
Yazarlar

Ceren Şahin Bu kişi benim

Gökhan Ünal Bu kişi benim

Feyza Arıcıoğlu

Yayımlanma Tarihi 25 Nisan 2014
Gönderilme Tarihi 25 Nisan 2014
Yayımlandığı Sayı Yıl 2014 Cilt: 4 Sayı: 1

Kaynak Göster

APA Şahin, C., Ünal, G., & Arıcıoğlu, F. (2014). Akt-GSK-3 ilişkisi: İki ayrı yolak iki ayrı hastalık. Clinical and Experimental Health Sciences, 4(1), 51-57.
AMA Şahin C, Ünal G, Arıcıoğlu F. Akt-GSK-3 ilişkisi: İki ayrı yolak iki ayrı hastalık. Clinical and Experimental Health Sciences. Aralık 2014;4(1):51-57.
Chicago Şahin, Ceren, Gökhan Ünal, ve Feyza Arıcıoğlu. “Akt-GSK-3 ilişkisi: İki Ayrı Yolak Iki Ayrı hastalık”. Clinical and Experimental Health Sciences 4, sy. 1 (Aralık 2014): 51-57.
EndNote Şahin C, Ünal G, Arıcıoğlu F (01 Aralık 2014) Akt-GSK-3 ilişkisi: İki ayrı yolak iki ayrı hastalık. Clinical and Experimental Health Sciences 4 1 51–57.
IEEE C. Şahin, G. Ünal, ve F. Arıcıoğlu, “Akt-GSK-3 ilişkisi: İki ayrı yolak iki ayrı hastalık”, Clinical and Experimental Health Sciences, c. 4, sy. 1, ss. 51–57, 2014.
ISNAD Şahin, Ceren vd. “Akt-GSK-3 ilişkisi: İki Ayrı Yolak Iki Ayrı hastalık”. Clinical and Experimental Health Sciences 4/1 (Aralık 2014), 51-57.
JAMA Şahin C, Ünal G, Arıcıoğlu F. Akt-GSK-3 ilişkisi: İki ayrı yolak iki ayrı hastalık. Clinical and Experimental Health Sciences. 2014;4:51–57.
MLA Şahin, Ceren vd. “Akt-GSK-3 ilişkisi: İki Ayrı Yolak Iki Ayrı hastalık”. Clinical and Experimental Health Sciences, c. 4, sy. 1, 2014, ss. 51-57.
Vancouver Şahin C, Ünal G, Arıcıoğlu F. Akt-GSK-3 ilişkisi: İki ayrı yolak iki ayrı hastalık. Clinical and Experimental Health Sciences. 2014;4(1):51-7.
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