Protein kinase C inhibitors: Rationale for use and potential in the treatment of bipolar disorder

CNS Drugs

Volumn 23, Issue 7, 2009, Pages 569-582

  Zarate, Carlos A ^a,b,c   Manji, Husseini K ^a,b  

^a Laboratory of Molecular Pathophysiology and Experimental Therapeutics   (United States)

^b NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^c Mark O Hatfield CRC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

7 HYDROXYSTAUROSPORINE; BRYOSTATIN; CARBAMAZEPINE; CURCUMIN; ENZASTAURIN; ISIS 3521; LITHIUM; LORAZEPAM; MEDROXYPROGESTERONE ACETATE; MIDOSTAURIN; PROTEIN KINASE C; PROTEIN KINASE C INHIBITOR; TAMOXIFEN; VALPROIC ACID;

ADD ON THERAPY; ANOREXIA; BIPOLAR DISORDER; BIPOLAR MANIA; BRAIN REGION; DISEASE ASSOCIATION; DRUG DOSE ESCALATION; DRUG TOLERABILITY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME SPECIFICITY; HUMAN; LONG TERM CARE; MANIA; MORBIDITY; MORTALITY; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TREATMENT OUTCOME; TREATMENT RESPONSE;

ANIMALS; ANTIMANIC AGENTS; BIPOLAR DISORDER; CLINICAL TRIALS AS TOPIC; HUMANS; MODELS, BIOLOGICAL; PROTEIN KINASE C; PROTEIN KINASE INHIBITORS;

EID: 67649406123     PISSN: 11727047     EISSN: 11791934     Source Type: Journal    
DOI: 10.2165/00023210-200923070-00003     Document Type: Review

References (81)

1. Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry 2007; 64 (5): 543-52
2. Gitlin M. Treatment-resistant bipolar disorder. Mol Psychiatry 2006; 11 (3): 227-40
3. Manji HK, Zarate CA. Molecular and cellular mechanisms underlying mood stabilization in bipolar disorder: implications for the development of improved therapeutics. Mol Psychiatry 2002; 7 Suppl. 1: S1-7
4. Zarate Jr CA, Singh J, Manji HK. Cellular plasticity cascades: targets for the development of novel therapeutics for bipolar disorder. Biol Psychiatry 2006; 59 (11): 1006-20
5. Casabona G. Intracellular signal modulation: a pivotal role for protein kinase C. Prog Neuropsychopharmacol Biol Psychiatry 1997; 21 (3): 407-25
6. Tanaka C, Nishizuka Y. The protein kinase C family for neuronal signaling. Annu Rev Neurosci 1994; 17: 551-67
7. Serova M, Ghoul A, Benhadji KA, et al. Preclinical and clinical development of novel agents that target the protein kinase C family. Semin Oncol 2006; 33 (4): 466-78
8. Toker A. Signaling through protein kinase C. Front Biosci 1998; 3: D1134-47
9. Mellor H, Parker PJ. The extended protein kinase C superfamily. Biochem J 1998; 332 (Pt 2): 281-92
10. Takai Y, Kishimoto A, Inoue M, et al. Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues I: purification and characterization of an active enzyme from bovine cerebellum. J Biol Chem 1977; 252 (21): 7603-9
11. Huang KP, Nakabayashi H, Huang FL. Isozymic forms of rat brain Ca2+-activated and phospholipid-dependent protein kinase. Proc Natl Acad Sci U S A 1986; 83 (22): 8535-9
12. Mackay HJ, Twelves CJ. Targeting the protein kinase C family: are we there yet? Natl Rev Cancer 2007; 7 (7): 554-62
13. Churchill E, Budas G, Vallentin A, et al. PKC Isozymes in chronic cardiac disease: possible therapeutic targets? Annu Rev Pharmacol Toxicol 2008; 48: 569-99
14. Dempsey EC, Cool CD, Littler CM. Lung disease and PKCs. Pharmacol Res 2007; 55 (6): 545-59
15. Aksoy E, Goldman M, Willems F. Protein kinase C epsilon: a new target to control inflammation and immune-mediated disorders. Int J Biochem Cell Biol 2004; 36 (2): 183-8
16. Das Evcimen N, King GL. The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res 2007; 55 (6): 498-510
17. Calabrese B, Halpain S. Essential role for the PKC target MARCKS in maintaining dendritic spine morphology. Neuron 2005; 48 (1): 77-90
18. Craske ML, Fivaz M, Batada NN, et al. Spines and neurite branches function as geometric attractors that enhance protein kinase C action. J Cell Biol 2005; 170 (7): 1147-58
19. Hongpaisan J, Alkon DL. A structural basis for enhancement of long-term associative memory in single dendritic spines regulated by PKC. Proc Natl Acad Sci U S A 2007; 104 (49): 19571-6
20. Manji HK, Lenox RH. Ziskind-Somerfeld Research Award. Protein kinase C signaling in the brain: molecular transduction of mood stabilization in the treatment of manicdepressive illness. Biol Psychiatry 1999; 46 (10): 1328-51
21. Einat H, Yuan P, Szabo ST, et al. Protein kinase C inhibition by tamoxifen antagonizes manic-like behavior in rats: implications for the development of novel therapeutics for bipolar disorder. Neuropsychobiology 2007; 55 (3-4): 123-31
22. Finlay JM, Zigmond MJ, Abercrombie ED. Increased dopamine and norepinephrine release in medial prefrontal cortex induced by acute and chronic stress: effects of diazepam. Neuroscience 1995; 64: 619-28
23. Birnbaum SG, Yuan PX, Wang M, et al. Protein kinase C overactivity impairs prefrontal cortical regulation of working memory. Science 2004; 306: 882-4
24. Runyan JD, Moore AN, Dash PK. A role for prefrontal calcium-sensitive protein phosphatase and kinase activities in working memory. Learn Mem 2005; 12: 103-10
25. Arnsten AFT, Manji HK. Mania: a rational neurobiology. Future Neurol 2008; 3 (2): 125-31
26. Coyle JT, Duman RS. Finding the intracellular signaling pathways affected by mood disorder treatments. Neuron 2003; 38 (2): 157-60
27. Steketee JD. Injection of the protein kinase inhibitor H7 into the A10 dopamine region blocks the acute responses to cocaine: behavioral and in vivo microdialysis studies. Neuropharmacology 1993; 32 (12): 1289-97
28. Chen G, Manji HK, Hawver DB, et al. Chronic sodium valproate selectively decreases protein kinase C alpha and epsilon in vitro. J Neurochem 1994; 63 (6): 2361-4
29. Browman KE, Kantor L, Richardson S, et al. Injection of the protein kinase C inhibitor Ro31-8220 into the nucleus accumbens attenuates the acute response to amphetamine: tissue and behavioral studies. Brain Res 1998; 814 (1-2): 112-9
30. Kantor L, Gnegy ME. Protein kinase C inhibitors block amphetamine-mediated dopamine release in rat striatal slices. J Pharmacol Exp Ther 1998; 284 (2): 592-8
31. Jope RS. Anti-bipolar therapy: mechanism of action of lithium. Mol Psychiatry 1999; 4 (2): 117-28
32. Bitran JA, Potter WZ, Manji HK, et al. Chronic Li+ attenuates agonist- and phorbol ester-mediated Na+/H+ antiporter activity in HL-60 cells. Eur J Pharmacol 1990; 188 (4-5): 193-202
33. Giambalvo CT. Protein kinase C and dopamine transport: 2. Effects of amphetamine in vitro. Neuropharmacology 1992; 31 (12): 1211-22
34. Giambalvo CT. Protein kinase C and dopamine transport: 1. Effects of amphetamine in vivo. Neuropharmacology 1992; 31 (12): 1201-10
35. Friedman E, Hoau-Yan-Wang, Levinson D, et al. Altered platelet protein kinase C activity in bipolar affective disorder, manic episode. Biol Psychiatry 1993; 33 (7): 520-5
36. Gnegy ME, Hong P, Ferrell ST. Phosphorylation of neuromodulin in rat striatum after acute and repeated, intermittent amphetamine. Brain Res Mol Brain Res 1993; 20 (4): 289-98
37. Manji HK, Etcheberrigaray R, Chen G, et al. Lithium decreases membrane-associated protein kinase C in hippocampus: selectivity for the alpha isozyme. J Neurochem 1993; 61 (6): 2303-10
38. Manji HK, Bersudsky Y, Chen G, et al. Modulation of protein kinase C isozymes and substrates by lithium: the role of myo-inositol. Neuropsychopharmacology 1996; 15 (4): 370-81
39. Cervo L, Mukherjee S, Bertaglia A, et al. Protein kinases A and C are involved in the mechanisms underlying consolidation of cocaine place conditioning. Brain Res 1997; 775 (1-2): 30-6
40. Birnbaum SG, Yuan PX, Wang M, et al. Protein kinase C overactivity impairs prefrontal cortical regulation of working memory. Science 2004; 306 (5697): 882-4
41. Wang HY, Friedman E. Lithium inhibition of protein kinase C activation-induced serotonin release. Psychopharmacology (Berl) 1989; 99 (2): 213-8
42. Lenox RH, Watson DG, Patel J, et al. Chronic lithium administration alters a prominent PKC substrate in rat hippocampus. Brain Res 1992; 570 (1-2): 333-40
43. Steketee JD. Intra-A10 injection of H7 blocks the development of sensitization to cocaine. Neuroreport 1994; 6 (1): 69-72
44. Wang HY, Friedman E. Enhanced protein kinase C activity and translocation in bipolar affective disorder brains. Biol Psychiatry 1996; 40 (7): 568-75
45. Watson DG, Lenox RH. Chronic lithium-induced downregulation of MARCKS in immortalized hippocampal cells: potentiation by muscarinic receptor activation. J Neurochem 1996; 67 (2): 767-77
46. Wang HY, Markowitz P, Levinson D, et al. Increased membrane-associated protein kinase C activity and translocation in blood platelets from bipolar affective disorder patients. J Psychiatr Res 1999; 33 (2): 171-9
47. Hahn CG, Friedman E. Abnormalities in protein kinase C signaling and the pathophysiology of bipolar disorder. Bipolar Disord 1999; 1 (2): 81-6
48. Soares JC, Chen G, Dippold CS, et al. Concurrent measures of protein kinase C and phosphoinositides in lithium-treated bipolar patients and healthy individuals: a preliminary study. Psychiatry Res 2000; 95 (2): 109-18
49. Wang HY, Johnson GP, Friedman E. Lithium treatment inhibits protein kinase C translocation in rat brain cortex. Psychopharmacology (Berl) 2001; 158 (1): 80-6
50. Wang H, Friedman E. Increased association of brain protein kinase C with the receptor for activated C kinase-1 (RACK1) in bipolar affective disorder. Biol Psychiatry 2001; 50 (5): 364-70
51. Kurita M, Nishino S, Ohtomo K, et al. Sodium valproate at therapeutic concentrations changes Ca2+ response accompanied with its weak inhibition of protein kinase C in human astrocytoma cells. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31 (3): 600-4
52. Pandey GN, Ren X, Dwivedi Y, et al. Decreased protein kinase C (PKC) in platelets of pediatric bipolar patients: effect of treatment with mood stabilizing drugs. J Psychiatr Res 2008; 42 (2): 106-16
53. Kulkarni J, Garland KA, Scaffidi A, et al. A pilot study of hormone modulation as a new treatment for mania in women with bipolar affective disorder. Psychoneuroendocrinology 2006; 31 (4): 543-7
54. Bebchuk JM, Arfken CL, Dolan-Manji S, et al. A preliminary investigation of a protein kinase C inhibitor in the treatment of acute mania. Arch Gen Psychiatry 2000; 57 (1): 95-7
55. Zarate Jr CA, Singh JB, Carlson PJ, et al. Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study. Bipolar Disord 2007; 9 (6): 561-70
56. Yildiz A, Guleryuz S, Ankerst DP, et al. Protein kinase C inhibition in the treatment of mania: a double-blind, placebo-controlled trial of tamoxifen. Arch Gen Psychiatry 2008; 65 (3): 255-63
57. Seelan RS, Khalyfa A, Lakshmanan J, et al. Deciphering the lithium transcriptome: microarray profiling of lithium-modulated gene expression in human neuronal cells. Neuroscience 2008; 151 (4): 1184-97
58. Lenox RH, et al. Myristoylated alanine-rich C kinase substrate (MARCKS): a molecular target for the therapeutic action of mood stabilizers in the brain? J Clin Psychiatry 1996; 57 Suppl. 13: 23-31
59. Iwata S, Hewlett GH, Gnegy ME. Amphetamine increases the phosphorylation of neuromodulin and synapsin I in rat striatal synaptosomes. Synapse 1997; 26 (3): 281-91
60. Iwata SI, Hewlett GH, Ferrell ST, et al. Enhanced dopamine release and phosphorylation of synapsin I and neuromodulin in striatal synaptosomes after repeated amphetamine. J Pharmacol Exp Ther 1997; 283 (3): 1445-52
61. Johnson DN. Effect of diazepam on food consumption in rats. Psychopharmacology (Berl) 1978; 56 (1): 111-2
62. Papp M, Willner P, Muscat R. An animal model of anhedonia: attenuation of sucrose consumption and place preference conditioning by chronic unpredictable mild stress. Psychopharmacology (Berl) 1991; 104 (2): 255-9
63. Aujla H, Beninger RJ. Intra-accumbens protein kinase C inhibitor NPC 15437 blocks amphetamine-produced conditioned place preference in rats. Behav Brain Res 2003; 147 (1-2): 41-8
64. Baum AE, Akula N, Cabanero M, et al. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry 2008; 13 (2): 197-207
65. Wellcome Trust Case Control Consortium. Genomewide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007; 447 (7145): 661-78
66. Jordan VC. Molecular mechanisms of antiestrogen action in breast cancer. Breast Cancer Res Treat 1994; 31 (1): 41-52
67. Horgan K, Cooke E, Hallett MB, et al. Inhibition of protein kinase C mediated signal transduction by tamoxifen: importance for antitumour activity. Biochem Pharmacol 1986; 35 (24): 4463-5
68. Couldwell WT, Weiss MH, DeGiorgio CM, et al. Clinical and radiographic response in a minority of patients with recurrent malignant gliomas treated with high-dose tamoxifen. Neurosurgery 1993; 32 (3): 485-9
69. Tang P, Roldan G, Brasher PM, et al. A phase II study of carboplatin and chronic high-dose tamoxifen in patients with recurrent malignant glioma. J Neurooncol 2006; 78 (3): 311-6
70. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994
71. Young RC, Biggs JT, Ziegler VE, et al. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 1978; 133: 429-35
72. Goldstein JA. Danazol and the rapid-cycling patient. J Clin Psychiatry 1986; 47 (3): 153-4
73. Lopez M, Lelliott CJ, Tovar S, et al. Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoA. Diabetes 2006; 55 (5): 1327-36
74. Cathcart CK, Jones SE, Pumroy CS, et al. Clinical recognition and management of depression in node negative breast cancer patients treated with tamoxifen. Breast Cancer Res Treat 1993; 27 (3): 277-81
75. Legha SS. Tamoxifen in the treatment of breast cancer. Ann Intern Med 1988; 109 (3): 219-28
76. Costanzo ES, Lutgendorf SK, Mattes ML, et al. Adjusting to life after treatment: distress and quality of life following treatment for breast cancer. Br J Cancer 2007; 97 (12): 1625-31
77. Gould TD, Quiroz JA, Singh J, et al. Emerging experimental therapeutics for bipolar disorder: insights from the molecular and cellular actions of current mood stabilizers. Mol Psychiatry 2004; 9 (8): 734-55
78. Catapano L, Manji H. Kinases as drug targets in the treatment of bipolar disorder. Drug Development Today 2008; 13: 295-302
79. Podar K, Raab MS, Chauhan D, et al. The therapeutic role of targeting protein kinase C in solid and hematologic malignancies. Expert Opin Investig Drugs 2007; 16 (10): 1693-707
80. Martinez A, Castro A, Medina M. Glycogen synthase kinase 3 (GSK-3) and its inhibitors. Hoboken (NJ): John Wiley & Sons, Inc., 2006
81. Tohen M. Clinical trials in bipolar mania: implications in study design and drug development. Arch Gen Psychiatry 2008; 65 (3): 252-3