Kinase inhibitors as potential therapeutics for acute and chronic neurodegenerative conditions

Current Pharmaceutical Design

Volumn 15, Issue 34, 2009, Pages 3919-3939

  Cuny, G D ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

Inhibitor; Kinase; Neurodegeneration; Phosphorylation; Selectivity

Indexed keywords

1,3,4 OXADIAZOLE DERIVATIVE; 4 [4 (4 FLUOROPHENYL) 5 (2 METHOXY 4 PYRIMIDINYL) 1 IMIDAZOLYL]CYCLOHEXANOL; APOPTOSIS SIGNAL REGULATING KINASE 1; CARRIER PROTEIN; CASEIN KINASE I; CASEIN KINASE II; COPPER ZINC SUPEROXIDE DISMUTASE; CYCLIN DEPENDENT KINASE 5; DEATH ASSOCIATED PROTEIN KINASE; EPHRIN RECEPTOR B3; FASUDIL; GLYCOGEN SYNTHASE KINASE 3; IMATINIB; LEUCINE RICH REPEAT KINASE 2; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 10; MITOGEN ACTIVATED PROTEIN KINASE P38; MIXED LINEAGE KINASE; PHOSPHOTRANSFERASE INHIBITOR; PODOPHYLLOTOXIN DERIVATIVE; PROTEIN KINASE C DELTA; PROTEIN KINASE N1; PROTEIN SERINE THREONINE KINASE; RECEPTOR INTERACTING PROTEIN 1; RHO ASSOCIATED COILED COILED CONTAINING KINASE II; ROSCOVITINE; ROTTLERIN; STRESS ACTIVATED PROTEIN KINASE INHIBITOR; TAU TUBULIN KINASE 1; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACUTE DISEASE; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; BINDING SITE; BRAIN EMBOLISM; BRAIN HEMORRHAGE; BRAIN ISCHEMIA; CEREBROVASCULAR ACCIDENT; CHRONIC DISEASE; CHRONIC MYELOID LEUKEMIA; DEGENERATIVE DISEASE; DEMYELINATION; DISEASE COURSE; DRUG BINDING; DRUG EFFICACY; DRUG STRUCTURE; DRUG TARGETING; ENTERITIS; ENZYME CONFORMATION; ENZYME INHIBITION; GASTROINTESTINAL STROMAL TUMOR; HUMAN; HUNTINGTON CHOREA; IC 50; MULTIPLE SCLEROSIS; NONHUMAN; OCCLUSIVE CEREBROVASCULAR DISEASE; OXIDATIVE STRESS; PARKINSON DISEASE; PNEUMONIA; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN PHOSPHORYLATION; PSORIASIS; REVIEW; RHEUMATOID ARTHRITIS; UNSPECIFIED SIDE EFFECT;

HUMANS; NEURODEGENERATIVE DISEASES; NEUROPROTECTIVE AGENTS; PHOSPHOTRANSFERASES;

EID: 70649098329     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161209789649330     Document Type: Review

References (222)

1. Green AR, Shuaib A. Therapeutic strategies for the treatment of stroke. Drug Discov Today 2006; 11: 681-693
2. Gennarelli TA, Graham DI. In: Silver JM, McAllister TW, Yudofsky SC, Eds. Textbook of Traumatic Brain Injury. Washington DC: American Psychiatric Publishing Inc. 2005; pp. 37-43.
3. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi MH. Forecasting the global burden of Alzheimer's disease. Alzheimer's Dement 2007; 3: 186-191 (Pubitemid 46825511)
4. Walsh DM, Selkoe DJ. A beta oligomers-a decade of discovery. J Neurochem 2007; 101: 1172-1184
5. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001; 60: 759-767 (Pubitemid 32678256)
6. Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, et al. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med 2008; 148: 379-397 (Pubitemid 351665469)
7. Greenamyre JT, Hastings TG. Biomedicine. Parkinson's-divergent causes, convergent mechanisms. Science 2004; 304: 1120-1122
8. Saito Y, Kawashima A, Ruberu NN, Fujiwara H, Koyama S, Sawabe M, et al. Accumulation of phosphorylated α-synuclein in aging human brain. J Neuropathol Exp Neurol 2003; 62: 644-654
9. Imarisio S, Carmichael J, Korolchuk V, Chen CW, Saiki S, Rose C, et al. Huntington's disease: from pathology and genetics to potential therapies. Biochem J 2008; 412: 191-209. (Pubitemid 351758226)
10. Nagai Y, Popiel HA. Conformational changes and aggregation of expanded polyglutamine proteins as therapeutic targets of the polyglutamine diseases: exposed beta-sheet hypothesis. Curr Pharm Des 2008; 14: 3267-3279
11. Strong MJ, Kesavapany S, Pant HC. The pathobiology of amyotrophic lateral sclerosis: a proteinopathy? J Neuropathol Exp Neurol 2005; 64: 649-664
12. Wada M, Uchihara T, Nakamura A, Oyanagi K. Bunina bodies in amyotrophic lateral sclerosis on Guam: a histochemical, immunohistochemical and ultrastructural investigation. Acta Neuropathol 1999; 98: 150-156 (Pubitemid 29355547)
13. Scott S, Kranz JE, Cole J, Lincecum JM, Thompson K, Kelly N, et al. Design, power, and interpretation of studies in the standard murine model of ALS. Amyotroph Lateral Scler 2008; 9: 4-15. (Pubitemid 351260367)
14. Compston A, Coles A. Mutiple sclerosis. Lancet 2002; 359: 1221-1231
15. Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 2007; 357: 851-862 (Pubitemid 47347319)
16. Spires-Jones TL, Stoothoff WH, de Calignon A, Jones PB, Hyman BT. Tau pathophysiology in neurodegeneration: a tangled issue. Trends Neurosci 2009; 32: 150-159
17. Mazanetz M, Fischer PM. Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases. Nat Rev Drug Discov 2007; 6: 464-479 (Pubitemid 47064569)
18. Lau L-F, Schachter JB, Seymour PA, Sanner MA. Tau protein phosphorylation as a therapeutic target in Alzheimer's disease. Curr Topic Med Chem 2002; 2: 395-415.
19. Neumann M, Kahle PJ, Giasson BI, Ozmen L, Borroni E, Spooren W, et al. Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha- synucleinopathies. J Clin Invest 2002; 110: 1429-1439 (Pubitemid 35396914)
20. Yankner BA, Lu T, Loerch P. The aging brain. Annu. Rev Pathol 2008; 3: 41-66.
21. Hucho F, Buchner K. Signal transduction and protein kinases: the long way from the plasma membrane into the nucleus. Naturwissenschaften 1997; 84: 281-290 (Pubitemid 27331817)
22. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S. The protein kinase complement of the human genome. Science 2002; 298: 1912-1934 (Pubitemid 35425239)
23. Walsh CT, Garneau-Tsodikova S, Gatto GJ Jr. Protein posttranslational modifications: the chemistry of proteome diversifications. Angew. Chem Int Ed Engl 2005; 44: 7342-7372 (Pubitemid 41689988)
24. Hanks SK, Hunter T. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J 1995; 9: 576-596
25. Hunter T. Protein kinase classification. Methods Enzymol 1991; 200: 3-37.
26. Wolanin PM, Thomason PA, Stock JB. Histidine protein kinases: key signal transducers outside the animal kingdom. Genome Biol 2002; 3: 3013.
27. Besant PG, Attwood PV. Mammalian histidine kinases. Biochim Biophys Acta 2005; 1754: 281-290
28. Bossemeyer D. Protein kinases-structure and function. FEBS 1995; 369: 57-61.
29. Oliver AW, Knapp S, Pearl LH. Activation segment exchange: a common mechanism of kinase autophosphylation? Trends Biochem Sci 2007; 32: 351-356
30. Barouch-Bentov R, Che J, Lee CC, Yang Y, Herman A, Jia Y, et al. A conserved salt bridge in the G loop of multiple protein kinases is important for catalysis and for in vivo Lyn function. Mol Cell 2009; 33: 43-52.
31. Jeffrey PD, Russo AA, Polyak K, Gibbs E, Hurwitz J, Massagué J, et al. Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex. Nature 1995; 376: 313-320
32. Otyepka M, Bártová I, Kříž Z, Koča J. Different mechanisms of cdk5 and cdk2 activation as revealed by cdk5/p25 and cdk2/cyclin A dynamics. J Biol Chem 2006; 281: 7271-7281 (Pubitemid 43847495)
33. Castoldi RE, Pennella G, Saturno, GS, Grossi P, Brughera M, Venturi M. Assessing and managing toxicities induced by kinase inhibitors. Curr Opin Drug Disc Develop 2007; 10: 53-57. (Pubitemid 46438257)
34. Wagey RTE, Krieger C. Abnormalities of protein kinases in neurodegenerative diseases. Prog Drug Res 1998; 31: 136-175
35. Cavalli A, Bolognesi ML, Minarini A, Rosini M, Tumiatti V, Recanatini M, et al. Multi-targeted-directed ligands to combat neurodegenerative diseases. J Med Chem 2008; 51: 347-372 (Pubitemid 351252260)
36. de Jonge MJA, Verweij J. Multiple targeted tyrosine kinase inhibition in the clinic: All for one or one for all? Eur J Cancer 2006; 42: 1351-1356
37. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, et al. A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 2008; 26: 127-132
38. McInnes C, Fischer PM. Strategies for the design of potent and selective kinase inhibitors. Curr Pharm Des 2005; 11: 1845-1863 (Pubitemid 40668139)
39. Akritopoulou-Zanze I. The identification of new protein kinase inhibitors as targets in modern drug discovery. IDrugs 2006; 9: 481-487 (Pubitemid 44018430)
40. Scapin G. Protein kinase inhibition: Different approaches to selective inhibitor design. Curr Drug Targets 2006; 7: 1443-1454 (Pubitemid 44718304)
41. Kiselyov A, Balakin KV, Tkachenko SE, Savchuk NP. Recent progress in development of non-ATP competitive small-molecule inhibitors of protein kinases. Mini-Rev Med Chem 2006; 6: 711-717 (Pubitemid 43881122)
42. Whitty A, Kumaravel G. Between a rock and hard place? Nat Chem Biol 2006; 2: 112-118
43. Clackson T, Wells JA. A hot spot of binding energy in a hormone-receptor interface. Science 1995; 267: 383-386
44. Arkin MR, Randal M, Delano WL, Hyde J, Luong TN, Oslob JD, et al. Binding of small molecules to an adaptive protein-protein interface. Proc Natl Acad Sci USA 2003; 100: 1603-1608 (Pubitemid 36254494)
45. Bogoyevitch MA, Barr RK, Ketterman AJ. Peptide inhibitors of protein kinases-discovery, characterisation and use. Biochim Biophys Acta 2005; 1754: 79-99. (Pubitemid 41797689)
46. Liu Y, Gray NS. Rational design of inhibitors that bind to inactive kinase conformations. Nat Chem Biol 2006; 2: 358-364 (Pubitemid 43936934)
47. Schindler T, Bornmann W, Pellicena P, Miller WT, Clarkson B, Kuriyan J. Structural mechanism for STI-571 inhibition of Abelson tyrosine kinase. Science 2000; 289: 1938-1942 (Pubitemid 30704121)
48. Noble ME, Endicott JA, Johnson LN. Protein kinase inhibitors: insights into drug design from structure. Science 2004; 303: 1800-1805 (Pubitemid 38374863)
49. Adams JA. Kinetic and catalytic mechanisms of protein kinases. Chem Rev 2001; 101; 2271-2290
50. LoGrasso PV, Frantz B, Rolando AM, O'Keefe SJ, Hermes JD, O'Neill EA. Kinetic mechanism of p38 MAP kinase. Biochemistry 1997; 36: 10422-10427 (Pubitemid 27374134)
51. Chen G, Porter MD, Bristol JR, Fitzgibbon MJ, Pazhanisamy S. Kinetic mechanism of the p38-α MAP kinase: phosphoryl transfer to synthetic peptides. Biochemistry 2000; 39: 2079-2087
52. Ohren JF, Chen H, Pavlovsky A, Whitehead C, Zhang E, Kuffa P, et al. Structure of human MAP kinase kinase 1 (MEK1) and MEK2 decribe novel noncompetitive kinase inhibition. Nat Struct Mol Biol 2004; 11: 1192-1197
53. Zheng J, Trafny EA, Knighton DR, Xuong NH, Taylor SS, Ten Eyck LF, et al. 2.2 Å refined crystal structure of the catalytic subunit of cAMP-dependent protein kinase complexed with MnATP and a peptide inhibitor. Acata Crystallogr D 1993; 49: 362-365
54. Bogoyevich MA, Boehm I, Oakley A, Ketterman AJ, Barr RK. Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential. Biochim Biophys Acta 2004; 1697: 89-101. (Pubitemid 38326764)
55. Gupta S, Barrett T, Whitmarsh AJ, Cavenagh J, Sluss HK, Dérijard B, et al. Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J 1996; 15: 2760-2770 (Pubitemid 26176253)
56. Whitmarch AJ, Cavanagh J, Tournier C, Yasuda J, Davis RJ. A mammalian scaffold complex that selectively mediates MAP kinase activation. Science 1998; 281: 1671-1674 (Pubitemid 28435582)
57. Borsello T, Forloni G. JNK signaling: A possible target to prevent neurodegeneration. Curr Pharm Des 2007; 13: 1875-1886 (Pubitemid 47010160)
58. Resnick L, Fennell M. Targeting JNK3 for the treatment of neurodegenerative disorders. Drug Discov Today 2004; 9: 932-939 (Pubitemid 39389054)
59. Harper SJ, LoGrasso P. Inhibitors of the JNK signaling pathway. Drugs Fut 2001; 26: 957-973
60. Yang DD, Kuan C-Y, Whitmarsh AJ, Rincon M, Zheng TS, Davis RJ, et al. Absence of excitotoxicity induced apoptosis in the hippocampus of mice lacking the Jnk 3 gene. Nature 1997; 389: 865-870 (Pubitemid 27462982)
61. Kuan C-Y, Whitmarsh AJ, Yang DD, Liao G, Schloemer AJ, Dong C, et al. A critical role of neural-specific JNK3 for ischemic apoptosis. Proc Natl Acad Sci USA 2003; 100: 15184-15189 (Pubitemid 37518037)
62. Ries V, Silva RM, Oo TF, Cheng HC, Rzhetskaya M, Kholodilov N, et al. JNK2 and JNK3 combined are essential for apoptosis in dopamine neurons of the substantia nigra, but are not required for axon degeneration. J Neurochem 2008; 107: 1578-1588
63. Hunot S, Vila M, Teismann P, Davis RJ, Hirsch EC, Przedborski S, et al. JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease. Proc Nalt Acad Sci USA 2004; 101: 665-670 (Pubitemid 38084694)
64. Graczyk PP, Khan A, Bhatia GS, Palmer V, Medland D, Numata H, et al. The neuroprotective action of JNK3 inhibitors based on the 6,7-dihydro-5H-pyrrolo[1, 2-a]imidazole scaffold. Bioorg Med Chem Lett 2005; 15: 4666-4670
65. Christopher JA, Atkinson FL, Bax BD, Brown MJB, Champigny AC, Chuang TT, et al. 1-Aryl-3,4-dihydroisoquinoline inhibitors of JNK3. Bioorg Med Chem Lett 2009; 19: 2230-2234
66. Kamenecka T, Habel J, Duckett D, Chen W, Ling YY, Frackowiak B, et al. Stucture activity relationship and x-ray structures describing the selectivity of amino-pyrazole inhibitors for c-jun-N-terminal kinase 3 (JNK3) over p38. J Biol Chem 2009; in press.
67. Stebbins JL, De SK, Machleidt T, Becattini B, Vazquez J, Kuntzen C, et al. Identification of a new JNK inhibitor targeting the JNK-JIP interaction site. Proc Natl Acad Sci USA 2008; 105: 16809-16813
68. Barone FC, Parsons AA. Therapeutic potential of anti-inflammatory drugs for focal stroke. Exp Opin Invest Drugs 2000; 9: 2281-2306
69. Irving EA, Barone FC, Reith AD, Hadingham SJ, Parsons AA. Differential activation of MAPK/ERK and p38/SAPK in neurons and glia following focal cerebral ischemia in the rat. Mol Brain Res 2000; 77: 65-75.
70. Barone FC, Feuerstein GZ, White RF, Irving EA, Parsons AA, Hadingham SJ, et al. Selective inhibition of p38 mitogen activated kinase reduces brain injury and neurological deficits in rat focal stroke models. J Cereb Blood Flow Metab 1999; 19(Suppl 1): S613.
71. Barone FC, Irving EA, Ray AM, Lee JC, Kassis S, Kumar S, et al. Inhibition of p38 mitogen-activated protein kinase provides neuroprotection in cerebral focal ischemia. Med Chem Rev 2001; 21: 129-145 (Pubitemid 32185244)
72. Munoz L, Ranaivo HR, Roy SM, Hu W, Craft JM, McNamara LK, et al. A novel p38 alpha MAPK inhibitor suppresses brain proinflammatory cytokine up-regultion and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model. J Neuroinflamm 2007; 4: 21. (Pubitemid 47570621)
73. Goldstein DM, Gabriel T. Pathway to the clinic: Inhibition of p38 MAP kinase. A review of ten chemotypes selected for development. Curr Topic Med Chem 2005; 5: 1017-1029
74. Cheung ECC, Slack RS. Emerging role for ERK as a key regulator of neuronal apoptosis. Science's STKE 2004; 251: PE45
75. Colucci-D'Amato L, Perrone-Capano C, di Porzio U. Chronic activation of ERK and neurodegenerative diseases. BioEssays 2003; 25: 1085-1095 (Pubitemid 37411768)
76. Hasegawa M, Jakes R, Crowther RA, Lee VM, Ihara Y, Goedert M. Characterization of mAb AP422, a novel phosphorylation-dependent monoclonal antibody against tau protein. FEBS Lett 1996; 384: 25-30. (Pubitemid 26111925)
77. Perry G, Roder H, Nunomura A, Takeda A, Friedlich AL, Zhu X, et al. Activation of neuronal extracellular receptor kinase (ERK) in Alzheimer's disease links oxidative stress to abnormal phosphorylation. NeuroReport 1999; 10: 2411-2415 (Pubitemid 29367948)
78. Pei JJ, Braak H, An WL, Winblad B, Cowburn RF, Igbal K, et al. Up-regulation of mitogen-activated protein kinases ERK1/2 and MEK1/2 is associated with the progression of neurofibrillary degeneration in Alzheimer's disease. Mol Brain Res 2002; 109: 45-55.
79. Mori T, Wang X, Jung J-C. Mitogen-activated protein kinase inhibition in traumatic brain injury: in vitro and in vivo effects. J Cerebral Blood Flow Metab 2002; 22: 444-452 (Pubitemid 34273600)
80. Ohori M, Kinoshita T, Okubo M, Sato K, Yamazaki A, Arakawa H, et al. Identification of a selective ERK inhibitor and structural determination of the inhibitor-ERK2 complex. Biochem Biophys Res Commun 2005; 336: 357-363 (Pubitemid 41253441)
81. Anantharam V, Kitazawa M, Wagner J, Kaul S, Kanthasamy AG. Caspase-3-dependent proteolytic cleavage of protein kinase Cdelta is essential for oxidative stress-mediated dopaminergic cell death after exposure to methylcyclopetadienyl manganese tricarbonyl. J Neurosci 2002; 22: 1738-1751 (Pubitemid 35386292)
82. Kaul S, Kanthasamy A, Kitazawa M, Anantharam V, Kanthasamy AG. Caspase-3 dependent proteolytic activation of protein kinase Cdelta mediates and regulates 1-methyl-4-phenylpyrimidinium (MPP+)-induced cell death in dopaminergic cells: relevance to oxidative stress in dopaminergic degeneration. Eur J Neurosci 2003; 18: 1387-1401 (Pubitemid 37215094)
83. Zhang D, Anantharam V, Kanthasamy A, Kanthasamy AG. Neuroprotective effect of protein kinase Cδ inhibitor rottlerin in cell culture and animal models of Parkinson's disease. J Pharmacol Exp Ther 2007; 322: 913-922 (Pubitemid 47295809)
84. Soltoff SP. Rottlerin: an inappropriate and ineffective inhibitor of PKCδ. Trends Pharm Sci 2007; 28: 453-458
85. Hashimoto R, Nakamura Y, Kosako H, Amano M, Kaibuchi K, Inagaki M, et al. Distribution of Rho-kinase in the bovine brain. Biochem Biophys Res Commun 1999; 263: 575-579
86. Amano M, Chihara K, Nakamura N, Kanek T, Matsuura Y, Kaibuchi K. The COOH terminus of Rho-kinase negatively regulates Rho-kinase activity. J Biol Chem 1999; 274: 32418-32424 (Pubitemid 129503845)
87. Riento K, Ridley A. ROCKs: multifunctional kinases in cell behavior. Nat Rev Mol Cell Biol 2003; 4: 446-456 (Pubitemid 36648590)
88. Bishop A, Hall A. Rho GTPases and their effector proteins. Biochem J 2000; 348; 241-255
89. Fu X, Gong MC, Jia T, Somlyo AV, Somlyo AP. The effects of the Rho-kinase inhibitor Y-27632 on arachidonic acid-, GTP S-, and phorbol ester-induced Ca-sensitization of smooth muscle. FEBS Lett 1998; 440: 183-187
90. 2+ sensitization in the bovine cerebral artery: unimportant role for protein kinase C. Circ Res 2002; 91: 112-119
91. Brabeck C, Beschorner R, Conrad S, Mittelbronn M, Bekure K, Meyermann R, et al. Lesional expression of RhoA and RhoB following traumatic brain injury in humans. J Neurotrauma 2004; 21: 697-706. (Pubitemid 38880242)
92. Amano M, Kaneko T, Maeda A, Nakayama M, Ito M, Yamauchi T, et al. Identification of Tau and MAP2 as novel substrates of Rho-kinase and myosin phosphatase. J Neurochem 2003; 87: 780-790 (Pubitemid 37310643)
93. Honing H, van den Berg TK, van der Pol SM, Dijkstra CD, van der Kammen RA, Collard JG, et al. RhoA activation promotes transendothelial migration of monocytes via ROCK. J Leukoc Biol 2004; 75: 523-528 (Pubitemid 38316384)
94. Mueller BK, Mack H, Teusch N. Rho kinase, a promising drug target for neurological disorders. Nat Rev Drug Discov 2005; 4: 387-398 (Pubitemid 40704122)
95. Sasaki Y, Suzuki M, Hidaka H. The novel and specific Rho-kinase inhibitor (S)-(+)-2-methyl-1-[(4-methyl-5-isoquinoline)sulfonyl]-homopiperazine as a probing molecule for Rho-kinase-involved pathway. Pharm Ther 2002; 93: 225-232
96. Dajani R, Fraser E, Roe SM, Young N, Good V, Dale TC, et al. Crystal structure of glycogen synthase kinase 3β: Structural basis for phosphate-primed substrate specificity and autoinhibition. Cell 2001; 105: 721-732 (Pubitemid 32635102)
97. Cohen P, Goedert M. GSK3 inhibitors: development and therapeutic potential. Nat Rev Drug Discov 2004; 3: 479-487 (Pubitemid 38807530)
98. Avila J, Hernández F. GSK-3 inhibitors for Alzheimer's disease. Expert Rev Neurotherapeutics 2007; 7: 1527-1533
99. Hooper C, Killick R, Lovestone S. The GSK3 hypothesis of Alzheimer's disease. J Neurochem 2008; 104: 1433-1439
100. Song JS, Yang SD. Tau protein kinase I/GSK-3β/kinase FA in heparin phosphorylates tau on Ser199, Thr231, Ser235, Ser262, Ser369, and Ser400 sites phosphorylated in Alzheimer disease brain. J Protein Chem 1995; 14: 95-105.
101. Carmichael J, Sugars KL, Bao YP, Rubinsztein DC. Glycogen synthase kinase-3β inhibitors prevent cellular polyglutamine toxicity caused by the Huntington's disease mutation. J Biol Chem 2002; 277: 33791-33798 (Pubitemid 35056190)
102. Koh S-H, Kim Y, Kim HY, Hwang S, Lee CH, Kim SH. Inhibition of glycogen synthase kinase-3 suppresses the onset of symptoms and disease progression of G93A-SOD1 mouse model of ALS. Exp Neurol 2007; 205: 336-346 (Pubitemid 46755762)
103. Noble W, Planel E, Zehr C, Olm V, Meyerson J, Suleman F, et al. Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced taupathy and degeneration in vivo. Proc Nalt Acad Sci USA 2005; 102: 6990-6995
104. Aghdam SY, Barger SW. Glycogen synthase kinase-3 in neurodegeneration and neuroprotection: lessons from lithium. Curr Alzheimer's Res 2007; 4: 21-31.
105. Coghlan MP, Culbert AA, Cross DA, Corcoran SL, Yates JW, Pearce NJ, et al. Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. Chem Biol 2000; 7: 793-803.
106. Hu S, Begum AN, Jones MR, Oh MS, Beech WK, Beech BH, et al. GSK3 inhibitors show benefits in an Alzheimer's disease (AD) model of neurodegeneration but adverse effects in control animals. Neurobiol Dis 2009; 33: 193-206.
107. Bain J, McLauchlan H, Elliot M, Cohen P. The specificities of protein kinase inhibitors: an update. Biochem J 2003; 371: 199-204. (Pubitemid 36458094)
108. Leclerc S, Garnier M, Hoessel R, Marko D, Bibb JA, Snyder GL, et al. Indirubins inhibit glycogen synthase kinase-3β and cdk5/p25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. J Biol Chem 2001; 276: 251-260
109. Saitoh M, Kunitomo J, Kimura E, Hayase Y, Kobayashi H, Uchiyama N, et al. Design, synthesis and structure-activity relationship of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta. Bioorg Med Chem 2009; 17: 2017-2029
110. Malumbres M, Barbacid M. Mammalian cyclin-dependent kinases. Trends Biochem Sci 2005; 30: 630-641
111. Knockaert M, Greengard P, Meijer L. Pharmacological inhibitors of cyclin-dependent kinases. Treands Pharm Sci 2002; 23: 417-425
112. Lew J, Huang QQ, Qi Z, Winkfein RJ, Aebersold R, Hunt T, et al. A brain-specific activator of cyclin-dependent kinase 5. Nature 1994; 371: 423-426
113. Ishiguro K, Kobayashi S, Omori A, Takamatsu M, Yonekura S, Anzai K, et al. Identification of the 23 kDa subunit of tau protein kinase II as a putative activator of cdk5 in bovine brain. FEBS Lett 1994; 342: 203-208 (Pubitemid 24115197)
114. Tsai LH, Delalle I, Caviness VS Jr, Chae T, Harlow E. p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature 1994; 371: 419-423 (Pubitemid 24302556)
115. Sharma P, Steinbach PJ, Sharma M, Amin ND, Barchi JJ Jr, Pant HC. Identification of substrate binding site of cyclin-dependent kinase 5. J Biol Chem 1999; 274: 9600-9606 (Pubitemid 129517936)
116. Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH. Conversion of p35 to p25 deregulates cdk5 activity and promotes neurodegeneration. Nature 1999; 402: 615-622 (Pubitemid 129516324)
117. Kusakawa G, Saito T, Onuki R, Ishiguro K, Kishimoto T, Hisanaga S. Calpain-dependent proteolytic cleavage of the p35 cyclin-dependent kinase 5 activator to p25. J Biol Chem 2000; 275: 17166-17172 (Pubitemid 30398964)
118. nck5a complex. Mol Cell 2001; 8: 657-669
119. Liu M, Choi S, Cuny GD, Ding K, Dobson BC, Glicksman MA, et al. Kinetic studies of cdk5/p25 kinase: Phosphorylation of tau and complex inhibition by two prototype inhibitors. Biochemistry 2008; 47; 8367-8377
120. Camins A, Verdaguer E, Folch J, Canudas AM, Pallàs M. The role of cdk5/p25 formation/inhibition in neurodegeneration. Drug News Perspect 2006; 19: 453-460
121. Shelton SB, Johnson GVW. Cyclin-dependent kinase-5 in neurodegeneration. J Neurochem 2004; 88: 1313-1326
122. Monaco EA III. Recent evidence regarding a role for cdk5 dysregulation in Alzheimer's disease. Curr Alzheimer Res 2004; 1: 33-38
123. Tandon A, Yu H, Wang L, Rogaeva E, Sato C, Chishi MA, et al. Brain levels of cdk5 activator p25 are not increased in Alzheimer's or other neurodegenerative diseases with neurofibrillary tangles. J Neurochem 2003; 86: 572-581 (Pubitemid 36897438)
124. Ahlijanian MK, Barrezueta NX, Williams RD, Jakowski A, Kowsz KP, McCarthy S, et al. Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, and activator of cdk5. Proc Natl Acad Sci USA 2000; 97: 2910-2915 (Pubitemid 30159271)
125. Noble W, Olm V, Takata K, Casey E, Mary O, Meyerson J, et al. Cdk5 is a key factor in tau aggregation and tangle formation in vivo. Neuron 2003; 38: 555-565 (Pubitemid 36645031)
126. Sun K-H, de Pablo Y, Vincent F, Shah K. Deregulated cdk5 promotes oxidative stress and mitochondrial dysfunction. J Neurochem 2008; 107: 265-278
127. Wen Y, Yang S-H, Liu R, Perez EJ, Brun-Zinkernagel AM, Koulen P, et al. Cdk5 is involved in NFT-like tauopathy induced by transient cerebral ischemia in female rats. Biochim Biophys Acta 2007; 1772: 473-483 (Pubitemid 46400382)
128. Weishaupt JH, Kussmaul L, Grötsch P, Heckel A, Rohde G, Romig H. et al. Inhibition of cdk5 is protective in necrotic and apoptotic paradigms of neuronal cell death and prevents mitochondrial dysfunction. Mol Cell Neurosci 2003; 24: 489-502. (Pubitemid 37311311)
129. Schneider A, Araújo GW, Trajkovic K, Herrmann MM, Merkler D, Mandelkow EM, et al. Hyperphosphorylated and aggregation of tau in experimental autoimmune encephalomyelitis. J Biol Chem 2004; 279: 55833-55839 (Pubitemid 40066591)
130. Paoletti P, Vila I, Rifé M, Lizcano JM, Alberch J, Ginés S. Dopaminergic and glutamatergic signaling crosstalk in Huntington's disease neurodegeneration: the role of p25/cyclin-dependent kinase 5. J Neurosci 2008; 28: 10090-10101
131. Smith PD, Crocker SJ, Jackson-Lewis V, Jordan-Sciutto KL, Hayley S, Mount MP. Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease. Proc Natl Acad Sci USA 2003; 100: 13650-13655 (Pubitemid 37444794)
132. Nguyen MD, Larivière RC, Julien J-P. Deregulation of cdk5 in a mouse model of ALS: Toxicity alleviated by perikaryal neurofilament inclusions. Neuron 2001; 30: 135-147
133. Mapelli M, Massimiliano L, Crovace C, Seeliger MA, Tsai L-H, Meijer L, et al. Mechanism of cdk5/p25 binding by cdk inhibitors. J Med Chem 2005; 48: 671-679 (Pubitemid 40209090)
134. Ahn JA, Radhakrishnan ML, Mapelli M, Choi S, Tidor B, Cuny GD, et al. Defining cdk5 ligand chemical space with small molecule inhibitors of tau phosphorylation. Chem Biol 2005; 12: 811-823 (Pubitemid 41009160)
135. Wang LH, Besirli CG, Johnson EM Jr. Mixed-lineage kinases: A target for the prevention of neurodegeneration. Annu. Rev Pharmacol Toxicol 2004; 44: 451-474
136. The Parkinson Study Group PRECEPT Investigators. Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease. Neurology 2007; 69: 1480-1490
137. Apostol BL, Simmons DA, Zuccato C, Illes K, Pallos J, Casale M, et al. CEP-1347 reduces mutant huntingtin-associated neurotoxicity and restores BDNF levels in R6/2 mice. Mol Cell Neurosci 2008; 39: 8-20.
138. Hudkins RL, Diebold JL, Tao M, Josef KA, Park CH, Angeles TS, et al. Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: Optimization, mixed-lineage kinase 1 cystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models. J Med Chem 2008; 51: 5680-5689
139. Pasquale EB. Eph receptor signaling casts a wide net on cell behavior. Nat Rev Mol Cell Biol 2005; 6: 462-475
140. Miao H, Strebhardt K, Pasquale EB, Shen T-L, Guan J-L, Wang B. Inhibition of integrin-mediated cell adhesion but not directional cell migration requires catalytic activity of EphB3 receptor tyrosine kinase. Role of Rho family small GTPases. J Biol Chem 2005; 280: 923-932
141. Kullander K, Mather NK, Diella F, Dottori M, Boyd AW, Klein R. Kinase-dependent and kinase-independent functions of EphA4 receptors in major axon tract formation in vivo. Neuron 2001; 29: 73-84. (Pubitemid 32108723)
142. Kullander K, Klein R. Mechanism and functions of Eph and Ephrin signalling. Nat Rev Mol Cell Biol 2002; 3: 475-486 (Pubitemid 34733429)
143. Pasquale EB. Eph-ephrin bidirectional signaling in physiology and disease. Cell, 2008; 133: 38-52.
144. Himanen JP, Saha N, Nikolov DB. Cell-cell signaling via Eph receptors and ephrins. Curr Opin Cell Biol 2007; 19: 534-542 (Pubitemid 350016850)
145. Aoto J, Chen L. Bidirectional ephrin/Eph signaling in synaptic functions. Brain Res 2007; 1184: 72-80. (Pubitemid 350160564)
146. Binns KL, Taylor PP, Sicheri F, Pawson T, Holland SJ. Phosphorylation of tyrosine residues in the kinase domain and juxtamembrane region regulates the biological and catalytic activites of Eph receptors. Mol Cell Biol 2000: 20; 4791-4805 (Pubitemid 30396126)
147. Holder N, Cooke J, Brennan C. The Eph receptor tyrosine kinases and the ephrins-roles in nervous system development. Eur J Neurosci 1998: 10; 405-408 (Pubitemid 28325463)
148. Willson CA, Foster RD, Onifer SM, Whittemore SR, Miranda JD. EphB3 receptor and ligand expression in the adult rat brain. J Mol Histol 2006: 37; 369-380 (Pubitemid 44885244)
149. Liu X, Hawkes E, Ishimaru T, Tran T, Sretavan DW. EphB3: an endogenous mediator of adult axonal plasticity and regrowth after CNS injury. J Neurosci 2006; 26: 3087-3101
150. Willson CA, Miranda JD, Foster RD, Onifer SM, Whittemore SR. Transection of the adult rat spinal cord upregulates EphB3 receptor and ligand expression. Cell Transplant 2003; 12: 279-290 (Pubitemid 36577005)
151. Miranda JD, White LA, Marcillo AE, Willson CA, Jagid J, Whittemore SR. Induction of Eph B3 after spinal cord injury. Exp Neurol 1999; 156: 218-222 (Pubitemid 29153000)
152. Gainer TG, Seyb KI, Ni J, Schuman ER, Case A, Lo DC, et al. Structure-activity relationship study of EphB3 receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett 2009, in press.
153. Stanger BZ, Leder P, Lee TH, Kim E, Seed B. RIP: a novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death. Cell 1995; 81: 513-523
154. Meylan E, Tschopp J. The RIP kinases: crucial integrators of cell stress. Trends Biochem Sci 2005; 30: 151-159 (Pubitemid 40332531)
155. Festjens N, Berghe TV, Cornelis S, Vandenabeele P. RIP1, a kinase on the crossroads of a cell's decision to live or die. Cell Death Diff 2007; 14: 400-410 (Pubitemid 46259948)
156. Ting AT, Pimentel-Muiños FX, Seed B. RIP mediates tumor necrosis factor receptor 1 activation of NF-κB but not FAS/APO-1-initiated apoptosis. EMBO J 1996; 15: 6189-6196 (Pubitemid 26397891)
157. Lin Y, Devin A, Rodriguez Y, Liu Z. Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev 1999; 13: 2514-2526 (Pubitemid 29489643)
158. Degterev A, Yuan J. Expansion and evolution of cell death programmes. Nat Rev Mol Cell Biol 2008; 9: 378-390 (Pubitemid 351574200)
159. Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, et al. Fas triggers a alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 2000; 1: 489-495
160. Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for
161. Teng X, Degterev A, Jagtap P, Xing X, Choi S, Denu R, et al. Structure-activity relationship study of novel necroptosis inhibitors. Bioorg Med Chem Lett 2005; 15: 5039-5044 (Pubitemid 41400181)
162. You Z, Savitz SI, Yang J, Degterev A, Yuan J, Cuny GD, et al. Necrostatin-1 reduces histopathology and improves functional outcome after controlled cortical impact in mice. J Cereb Blood Flow Metab 2008; 28: 1565-1573
163. Jagtap PG, Degterev A, Choi S, Keys H, Yuan J, Cuny GD. Structure-activity relationship study of tricyclic necroptosis inhibitors. J Med Chem 2007; 50: 1886-1895 (Pubitemid 46626598)
164. Teng X, Keys H, Jeevanandam A, Porco JA Jr, Degterev A, Yuan J, Cuny GD. Structure activity relationship study of [1,2,3] thiadiazole necroptosis inhibitors. Bioorg Med Chem Lett 2007; 17: 6836-6840
165. Teng X, Keys H, Degterev A, Yuan J, Cuny GD. Structure-activity relationship and liver microsome stability studies of pyrrole necroptosis inhibitors. Bioorg Med Chem Lett 2008; 17: 3219-3223
166. Wang K, Li J, Degterev A, Hsu E, Yuan J, Yuan C. Structure-activity relationship analysis of a novel necroptosis inhibitor, Necrostatin-5. Bioorg Med Chem Lett 2007; 17: 1455-1465 (Pubitemid 46240823)
167. Degterev A, Hitomi J, Germscheid M, Ch'en IL, Korkina O, Teng X, et al. Identification of RIP1 kinase as a specific cellular target of necrostatins. Nat Chem Biol 2008; 4: 313-321 (Pubitemid 351550892)
168. Cuny GD, Degterev A, Yuan J. Necroptosis-A novel cell death mechanism. Drug Future 2008; 33: 225-233 (Pubitemid 351567921)
169. Vandenabeele P, Declercq W, Vanden Berghe T. Necrotic cell death and 'necrostatins': now we can control cellular explosion. Trends Biochem Sci 2008; 33: 352-355
170. Ito G, Okai T, Fujino G, Takeda K, Ichijo H, Katada T, et al. GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease. Biochemistry 2007; 46: 1380-1388 (Pubitemid 46208485)
171. Miklossy J, Arai T, Guo J-P, Klegeris A, Yu S, McGeer EG, et al. LRRK2 expression in normal and pathologic human brain and in human cell lines. J Neuropathol Exp Neurol 2006; 65: 953-963 (Pubitemid 44521796)
172. Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simón J, van der Brug M, et al. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 2004; 44: 595-600. (Pubitemid 39531224)
173. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, et al. Mutations in LRRK2 cause autosomal-dominant Parkinsonism with pleomorphic pathology. Neuron 2004; 44: 601-607 (Pubitemid 39531225)
174. West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA, et al. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci USA 2005; 102: 16842-16847 (Pubitemid 41688864)
175. Smith WW, Pei Z, Jiang H, Moore DJ, Liang Y, West AB, et al. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc Natl Acad Sci USA 2005; 102: 18676-18681 (Pubitemid 43011285)
176. Greggio E, Singleton A. Kinase signaling pathways as potential targets in the treatment of Parkinson's disease. Future Drugs 2007; 4: 783-792 (Pubitemid 350261443)
177. Greggio E, Jain S, Kingsbury A, Bandopadhyay R, Lewis P, Kaganovich A, et al. Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. NeuroBiol Dis 2006; 23: 329-341 (Pubitemid 44097032)
178. Cookson MR, Dauer W, Dawson T, Fon EA, Shen J. The role of kinases in familial Parkinson's disease. J Neurosci 2007; 27: 11865-11868 (Pubitemid 350072099)
179. Mata IF, Wedemeyer WJ, Farrer M, Taylor JP, Gallo KA. LRRK2 in Parkinson's disease: protein domains and functional insights. Trends Neurosci 2006; 29: 286-293
180. Covy JP, Giasson BI. Identification of compounds that inhibit the kinase activity of leucine-rich repeat kinase 2. Biochem Biophys Res Commun 2009; 378, 473-477
181. Sato S, Cerny RL, Buescher JL, Ikezu T. Tau-tubulin kinase 1 (TTBK1), a neuron-specific tau kinase candidate, is involved in tau phosphorylation and aggregation. J Neurochem 2006; 98: 1573-1584 (Pubitemid 44200447)
182. Houlden H, Johnson J, Gardner-Thorpe C, Lashley T, Hernandez D, Worth P, et al. Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nat Genet 2007; 39: 1434-1436 (Pubitemid 350191351)
183. Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, et al. Mammalian thioredoxin is a direct inhibitor of apoptosis signaling-regulating kinase (ASK) 1. EMBO J 1998; 17: 2596-2606
184. Tobiume K, Saitoh M, Ichijo H. Activation of apoptosis signaling-regulating kinase 1 by the stress-inducing activating phosphorylation of pre-formed oligomer. J Cell Physiol 2002; 191: 95-104. (Pubitemid 34195221)
185. Noguchi T, Takeda K, Matsuzawa A, Saegusa K, Nakano H, Gohda J, et al. Recruitment of tumor necrosis factor receptor-associated factor family proteins to apoptosis signal-induced cell death. J Biol Chem 2005; 280: 37033-37040
186. Fujisawa T, Takeda K. ASK family proteins in stress response and disease. Mol Biotechnol 2007; 37: 13-18. (Pubitemid 350135898)
187. Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, et al. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science 1997; 275: 90-94 (Pubitemid 27020316)
188. Sekine Y., Takeda K, Ichijo H. The ASK1-MAP kinase signaling in ER stress and neurodegenerative diseases. Curr Mol Med 2006; 6: 87-97.
189. Nishitoh H, Kadowaki H, Nagai A, Maruyama T, Yokota T, Fukutomi H, et al. ALS-linked mutant SOD1 induced ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1. Genes Dev 2008; 22: 1451-1464 (Pubitemid 351793080)
190. Uchikawa O, Sakai N, Terao Y, Suzuki H. Fused heterocyclic compound. PCT Int. Appl 2008, WO200816131.
191. Litchfield DW. Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J 2003; 369: 1-15.
192. Meijer L, Thunnissen A-MWH, White AW, Garnier M, Nikolic M, Tsai L-H, et al. Inhibition of cyclic-dependent kinases, GSK-3β and CK1 by hymenialdisine, a marine sponge constituent. Chem Biol 2000; 7: 51-63. (Pubitemid 30141925)
193. Zandomeni R, Zandomeni MC, Shugar D, Weinmann R. Caisein kinase type II is involved in the inhibition by 5,6-dichloro-1-beta-D- ribofuranosylbenzimidazole of specific RNA polymerase II transcription. J Biol Chem 1986; 261: 3414-3419 (Pubitemid 17204962)
194. Okochi M, Walter J, Koyama A, Nakajo S, Baba M, Iwatsubo T, et al. Constitutive phosphorylation of the Parkinson's disease associated α-synuclein. J Biol Chem 2000; 275: 390-397 (Pubitemid 30038997)
195. Ishii A, Nonaka T, Taniguchi S, Saito T, Arai T, Mann D, et al. Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human α-synucein: Implications for α-synuceinopathies. FEBS Lett 2007; 581: 4711-4717 (Pubitemid 47418797)
196. Fujiwara H, Hasegawa M, Dohmae N, Kawashima A, Masliah E, Goldberg MS, et al. Alpha-synuclein is phosphorylated in synucleinopathy lesions. Nat Cell Biol 2002; 4: 160-164
197. Waxman EA, Giasson BI. Specificity and regulation of casein kinase-mediated phosphorylation of α-synuclein. J Neuropathol Exp Neurol 2008; 67: 402-416
198. Takahashi M, Ko L, Kulathingal J, Jiang P, Seviever D, Yen S-HC. Oxidative stress-induced phosphorylation, degradation and aggregation of α-synuclein are linked to upregulated CK2 and cathepsin D. Eur J Neurosci 2007; 26: 863-874 (Pubitemid 47274626)
199. Flajolet M, He G, Heiman M, Lin A, Nairn AC, Greengard P. Regulation of Alzheimer's disease amyloid-β formation by casein kinase 1. Proc Natl Acad Sci USA 2007; 104: 4159-4164 (Pubitemid 47181595)
200. Hasegawa M, Arai T, Nonaka T, Kametani F, Yoshida M, Hashizume Y, et al. Phosphorylated TDP-43 in frontaltemporal lobar degeneration and amyotrophic lateral sclerosis. Ann Neurol 2008; 64: 60-70.
201. Rena G, Bain J, Elliot M, Cohen P. D4476, a cell-permeant inhibitor of CK1, suppresses the site-specific phosphorylation and nuclear exclusion of FOXO1a. EMBO Rep 2004; 5: 60-65
202. Suzuki Y, Cluzeau J, Hara T, Hirasawa A, Tsujimoto G, Oishi S, et al. Structure-activity relationships of pyrazine-based CK2 inhibitors: synthesis and evaluation of 2,6-disubstituted pyrazines and 4,6-disubstituted pyrimidines. Arch Pharm 2008; 341: 554-561
203. Prudent R, Cochet C. New protein kinase CK2 inhibitors: Jumping out of the catalytic box. Chem Biol 2009; 16: 112-120
204. Laudet M, Moucadel V, Prudent R, Filhol O, Wong YS, Royer D, et al. Identification of chemical inhibitors of protein-kinase CK2 subunit interaction. Mol Cell Biochem 2008; 316: 63-69
205. Cohen O, Feinstein E, Kimchi A. DAP-kinase is a Ca2+/calmodulin- dependent, cytoskeletal-associated protein kinase, with cell death-inducing functions that depend on its catalytic activity. EMBO J 1997; 16: 998-1008. (Pubitemid 27113179)
206. Velentza AV, Schumacher AM, Watterson DM. Structure, activity, regulation and inhibitor discovery for a protein kinase associated with apoptosis and neuronal death. Pharmacol Ther 2002; 93: 217-224 (Pubitemid 34615562)
207. Sakagami H, Kondo H. Molecular cloning and developmental expression of a rat homologue of death-associated protein kinase in the nervous system. Brain Res Mol Brain Res1997; 52: 249-256
208. Shamloo M, Soriano L, Wieloch T. Nikolich K, Urfer R, Oksenberg D. Death-associated protein kinase is activated by dephosphorylation in response to cerebral ischemia. J Biol Chem 2005; 280: 42290-42299 (Pubitemid 43023200)
209. Velentza AV, Wainwright MS, Zasadzki M, Mirzoeva S, Schumacher AM, Haiech J, et al. An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase attenuates hypoxia-ischemia induced acute brain injury. Bioorg Med Chem Lett 2003; 13: 3465-3470 (Pubitemid 37141409)
210. Zalchvar E, Berissi H, Mizrachy L, Idelchuk Y, Koren I, Eisenstein M, et al. DAP-kinase-mediated phosphorylation on the BH3 domian of beclin 1 promotes dissociation of beclin1 from Bcl-XL and induction of autophagy. EMBO Rep 2009; 10: 285-292
211. Carloni S, Buonocore G, Balduini W. Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. NeuroBiol Dis 2008; 32: 329-339
212. Sarkar S, Rubinsztein DC. Small molecule enhancers of autophagy for neurodegenerative diseases. Mol BioSyst 2008; 4: 895-901.
213. Mukai H. The structure and function of PKN, a protein kinase having a catalytic domain homologous to that of PKC. J Biochem (Tokyo) 2003; 133: 17-27. (Pubitemid 36240974)
214. Mukai H, Toshimori M, Shibata H, Kitagawa M, Shimakawa M, Miyahara M, et al. PKN associates and phosphorylates the headrod domain of neurofilament protein. J Biol Chem 1996; 271: 9816-9822 (Pubitemid 26137395)
215. Sihag RK, Inagaki M, Yamaguchi T, Shea TB, Pant HC. Role of phosphorylation on the structural dynamics and function of type III and IV intermediate filaments. Exp Cell Res 2007; 313: 2098-2109 (Pubitemid 46842988)
216. Collard J-F, Cote F, Julian J-P. Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature 1995; 375: 61-64
217. Rothstein JD. Excitotoxicity and Neurodegeneration in amyotrophic lateral sclerosis. Clin Neurosci 1995-1996; 3: 348-359 (Pubitemid 27052169)
218. Rothstein JD, Van Kammen M, Levey AI, Martin LJ, Kuncl RW. Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 1995; 38: 73-84.
219. Manser C, Stevenson A, Banner S, Davies J, Tudor EL, Ono Y, et al. Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport. FEBS Lett 2008; 582: 2303-2308
220. Mischiati C, Melloni E, Corallini F, Milani D, Bergamini C, Vaccarezza M. Potential role of PKC inhibitors in the treatment of hematological malignancies. Curr Pharm Des 2008; 14(21): 2075-2084
221. Mishani E, Abourbeh G, Eiblmaier M, Anderson CJ. Imaging of EGFR and EGFR tyrosine kinase overexpression in tumors by nuclear medicine modalities. Curr Pharm Des 2008; 14(28): 2983-2998
222. Sharma PS, Sharma R, Tyagi T. Receptor tyrosine kinase inhibitors as potent weapons in war against cancers. Curr Pharm Des 2009; 15(7): 758-776