Mixed lineage kinase-c-jun N-terminal kinase signaling pathway: A new therapeutic target in Parkinson's disease

Movement Disorders

Volumn 20, Issue 6, 2005, Pages 653-664

  Silva, Robert M ^a   Kuan, Chia Yi ^b   Rakic, Pasko ^c   Burke, Robert E ^a  

^a Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain   (United States)

^b CINCINNATI CHILDREN S HOSPITAL RESEARCH FOUNDATION   (United States)

^c YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Apoptosis; Neurodegeneration; Neuroprotection; Programmed cell death

Indexed keywords

CEP 11004; CEP 1347; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE; MIXED LINEAGE KINASE; MIXED LINEAGE KINASE INHIBITOR; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN C JUN; STRESS ACTIVATED PROTEIN KINASE; UNCLASSIFIED DRUG; CARBAZOLE DERIVATIVE; INDOLE DERIVATIVE; NEUROPROTECTIVE AGENT;

APOPTOSIS; CELL DAMAGE; CELL DEATH; CLINICAL TRIAL; DEGENERATIVE DISEASE; DOPAMINERGIC NERVE CELL; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NERVE CELL NECROSIS; NERVE FIBER DEGENERATION; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; ANIMAL; BIOLOGICAL MODEL; BRAIN; DRUG EFFECT; METABOLISM; NERVE DEGENERATION; PATHOLOGY; PHYSIOLOGY;

ANIMALS; BRAIN; CARBAZOLES; CELL DEATH; HUMANS; INDOLES; JNK MITOGEN-ACTIVATED PROTEIN KINASES; MAP KINASE KINASE KINASES; MODELS, BIOLOGICAL; NERVE DEGENERATION; NEUROPROTECTIVE AGENTS; PARKINSON DISEASE; PROTO-ONCOGENE PROTEINS C-JUN; SIGNAL TRANSDUCTION;

EID: 22844445441     PISSN: 08853185     EISSN: None     Source Type: Journal    
DOI: 10.1002/mds.20390     Document Type: Review

References (112)

1. Glucksmann A. Cell deaths in normal vertebrate ontogeny. Biol Rev 1951;26:59-86
2. Hamburger V. History of the discovery of neuronal death in embryos. J Neurobiol 1992;23:1116-1123.
3. Oppenheim RW. Cell death during development of the nervous system. Annu Rev Neurosci 1991;14:453-501.
4. Johnson EM, Deckwerth TL. Molecular mechanisms of developmental neuronal death. Annu Rev Neurosci 1993;16:31-46.
5. Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995;267:1456-1462.
6. Ellis RE, Yuan J, Horvitz HR. Mechanisms and functions of cell death. Annu Rev Cell Biol 1991;7:663-698.
7. Sloviter RS, Sollas AL, Dean E, Neubort S. Adrenalectomy induced granule cell degeneration in the rat hippocampal dentate gyrus: characterization of an in vivo model of controlled neuronal death. J Comp Neurol 1993;330:324-336.
8. Sloviter RS, Dean E, Neubort S. Electron microscopic analysis of adrenalectomy induced hippocampal granule cell degeneration in the rat: apoptosis in the adult central nervous system. J Comp Neurol 1993;330:337-351.
9. Janec E, Burke RE. Naturally occurring cell death during postnatal development of the substantia nigra of the rat. Mol Cell Neurosci 1993;4:30-35.
10. Macaya A, Munell F, Gubits RM, Burke RE. Apoptosis in substantia nigra following developmental striatal excitotoxic injury. Proc Natl Acad Sci U S A 1994;91:8117-8121.
11. Marti MJ, James CJ, Oo TF, Kelly WJ, Burke RE. Early developmental destruction of terminals in the striatal target induces apoptosis in dopamine neurons of the substantia nigra. J Neurosci 1997;17:2030-2039.
12. Tatton NA, Kish SJ. In situ detection of apoptotic nuclei in the substantia nigra compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice using terminal deoxynucleotidyl transferase labelling and acridine orange. Neuroscience 1997;77:1037-1048.
13. Stefanis L, Burke RE, Greene LA. Apoptosis in neurodegenerative disorders. Curr Opin Neurol 1997;10:299-305.
14. Tompkins MM, Basgall EJ, Zamrini E, Hill WD. Apoptotic-like changes in Lewy-body-associated disorders and normal aging in substantia nigral neurons. Am J Pathol 1997;150:119-131.
15. Tatton NA, Maclean-Fraser A, Tatton WG, Perl DP, Olanow CW. A fluorescent double-labeling method to detect and confirm apoptotic nuclei in Parkinson's disease. Ann Neurol 1998;44:S142-S148.
16. Wullner U, Kornhuber J, Weller M, et al. Cell death and apoptosis regulating proteins in Parkinson's disease - a cautionary note. Acta Neuropathol (Berl) 1999;97:408-412.
17. Kosel S, Egensperger R, von Eitzen U, Mehraein P, Graeber MB. On the question of apoptosis in the parkinsonian substantia nigra. Acta Neuropathol (Berl) 1997;93:105-108.
18. Clarke PGH. Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol (Berl) 1990;181:195-213.
19. Yuan J, Yankner BA. Apoptosis in the nervous system. Nature 2000;407:802-809.
20. Mattson MP. Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 2000;1:120-129.
21. Vila M, Przedborski S. Targeting programmed cell death in neurodegenerative diseases. Nat Rev Neurosci 2003;4:365-375.
22. Hunot S, Vila M, Teismann P, et al. JNK-mediated induction of cyclooxygenase 2 is required for neurodegeneration in a mouse model of Parkinson's disease. Proc Natl Acad Sci U S A 2004; 101:665-670.
23. Kyriakis JM, Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 2001;81:807-869.
24. Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell 2000;103:239-252.
25. Kyriakis JM, Avruch J. pp54 microtubule-associated protein 2 kinase. A novel serine/threonine protein kinase regulated by phosphorylation and stimulated by poly-L-lysine. J Biol Chem 1990; 265:17355-17363.
26. Hibi M, Lin A, Smeal T, Minden A. Karin M. Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev 1993;7:2135-2148.
27. Kyriakis JM, Banerjee P, Nikolakaki E, et al. The stress-activated protein kinase subfamily of c-Jun kinases. Nature. 1994;369:156-160.
28. Derijard B, Hibi M, Wu IH, et al. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 1994;76:1025-1037.
29. Tournier C, Dong C, Turner TK, Jones SN, Flavell RA, Davis RJ. MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines. Genes Dev 2001;15:1419-1426.
30. Maroney AC, Finn JP, Connors TJ, et al. Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. J Biol Chem 2001;276:25302-25308.
31. Xu Z, Maroney AC, Dobrzanski P, Kukekov NV, Greene LA. The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis. Mol Cell Biol 2001;21:4713-4724.
32. Gallo KA, Johnson GL. Mixed-lineage kinase control of JNK and p38 MAPK pathways. Nat Rev Mol Cell Biol 2002;3:663-672.
33. Ganguly A, Oo TF, Rzhetskaya M, et al. CEP11004, a novel inhibitor of the mixed lineage kinases, suppresses apoptotic death in dopamine neurons of the substantia nigra induced by 6-hydroxy-dopamine. J Neurochem 2004;88:469-480.
34. Urano F, Wang X, Bertolotti A, et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000;287:664-666.
35. Musti AM, Treier M, Bohmann D. Reduced ubiquitin-dependent degradation of c-Jun after phosphorylation by MAP kinases. Science 1997;275:400-402.
36. Behrens A, Sibilia M, Wagner EF. Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation. Nat Genet 1999;21:326-329.
37. Tournier C, Hess P, Yang DD. et al. Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science 2000;288:870-874.
38. Maundrell K, Antonsson B, Magnenat E, et al. Bcl-2 undergoes phosphorylation by C-JUn N-terminal kinase/stress-activated protein kinases in the presence of the constitutively active GTP-binding protein Rac1. J Biol Chem 1997;272:25238-25242.
39. Yamamoto K, Ichijo H, Korsmeyer SJ. BCL-2 is phosphorylated and inactivated by an ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol 1999;19:8469-8478.
40. Kharbanda S, Saxena S, Yoshida K, et al. Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage. J Biol Chem 2000;275:322-327.
41. Donovan N, Becker EB, Konishi Y, Bonni A. JNK phosphorylation and activation of BAD couples the stress-activated signaling pathway to the cell death machinery. J Biol Chem 2002;277: 40944-40949.
42. Lei K, Davis RJ. JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci U S A 2003;100:2432-2437.
43. Dickens M, Rogers JS, Cavanagh J, et al. A cytoplasmic inhibitor of the JNK signal transduction pathway. Science 1997;277:693-696.
44. Tapon N, Nagata K, Lamarche N, Hall A. A new rac target POSH is an SH3-containing scaffold protein involved in the JNK and NF-kappaB signaling pathways. EMBO J 1998;17:1395-1404.
45. Whitmarsh AJ, Kuan CY, Kennedy NJ, et al. Requirement of the JIP1 scaffold protein for stress-induced JNK activation. Genes Dev 2001;15:2421-2432.
46. Xia XG, Harding T, Weller M, Bieneman A, Uney JB, Schulz JB. Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in the MPTP model of Parkinson's disease. Proc Natl Acad Sci U S A 2001;98:10433-10438.
47. Xu Z, Kukekov NV, Greene LA. POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis. EMBO J 2003;22:252-261.
48. Edwards SN, Tolkovsky AM. Characterization of apoptosis in cultured rat sympathetic neurons after nerve growth factor withdrawal. J Cell Biol 1994;124:537-546.
49. Martin DP, Schmidt RE, DiStefano P, Lowry O, Carter J. Johnson E. Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation. J Cell Biol 1988;106:829-844.
50. Deckwerth TL, Johnson EM. Temporal analysis of events associated with programmed cell death (apoptosis) of sympathetic neurons deprived of nerve growth factor. J Cell Biol 1993;123:1207-1222.
51. Ham J, Babij C, Whitfield J, et al. A c-jun dominant negative mutant protects sympathetic neurons against programmed cell death. Neuron 1995;14:927-939.
52. Estus S, Zaks WJ, Freeman RS, Gruda M, Bravo R, Johnson EM. Altered gene expression in neurons during programmed cell death identification of c-jun as necessary for neuronal apoptosis. J Cell Biol 1994;127:1717-1727.
53. Watson A, Eilers A, Lallemand D, Kyriakis J, Rubin LL, Ham J. Phosphorylation of c-Jun is necessary for apoptosis induced by survival signal withdrawal in cerebellar granule neurons. J Neurosci 1998;18:751-762.
54. Mesner PW, Winters TR, Green SH. Nerve growth factor withdrawal-induced cell death in neuronal PC12 cells resembles that in sympathetic neurons. J Cell Biol 1992;119:1669-1680.
55. Choi HK, Won LA, Kontur PJ, et al. Immortalization of embryonic mesencephalic dopaminergic neurons by sematic cell fusion. Brain Res 1991;552:67-76.
56. Holtz WA, O'Malley KL. Parkinsonian mimetics induce aspects of unfolded protein response in death of dopaminergic neurons. J Biol Chem 2003;278:19367-19377.
57. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases in apoptosis. Science 1995;270:1326-1331.
58. Eilers A, Whitfield J, Babij C, Rubin LL, Ham J. Role of the Jun kinase pathway in the regulation of c-Jun expression and apoptosis in sympathetic neurons. J Neurosci 1998;18:1713-1724.
59. Le Niculescu H, Bonfoco E, Kasuya Y, Claret FX, Green DR, Karin M. Withdrawal of survival factors results in activation of the JNK pathway in neuronal cells leading to Fas ligand induction and cell death. Mol Cell Biol 1999;19:751-763.
60. Mota M, Reeder M, Chernoff J, Bazenet CE. Evidence for a role of mixed lineage kinases in neuronal apoptosis. J Neurosci 2001; 21:4949-4957.
61. Knusel B, Hefti F. K-252 compounds: modulators of neurotrophin signal transduction. J Neurochem 1992;59:1987-1996.
62. Kase H, Iwahashi K, Nakanishi S. et al. K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases. Biochem Biophys Res Commmun 1987; 142:436-440.
63. Maroney AC, Lipfert L, Forbes ME, et al. K-252a induces tyrosine phosphorylation of the focal adhesion kinase and neurite outgrowth in human neuroblastoma SH-SY5Y cells. J Neurochem 1995;64: 540-549.
64. Borasio GD. Differential effects of the protein kinase inhibitor K-252a on the in vitro survival of chick embryonic neurons. Neurosci Lett 1990;108:207-212.
65. Goodman Y, Mattson MP. Staurosporine and K-252 compounds protect hippocampal neurons against amyloid beta-peptide toxicity and oxidative injury. Brain Res 1994;650:170-174.
66. Cheng B, Barger SW, Mattson MP. Staurosporine. K-252a, and K-252b stabilize calcium homeostasis and promote survival of CNS neurons in the absence of glucose. J Neurochem 1994;62: 1319-1329.
67. Kaneko M, Saito Y, Saito H, et al. Neurotrophic 3,9-bis[(alkyl-thio)methyl]-and-bis(alkoxymethyl)-K-252a derivatives. J Med Chem 1997;40:1863-1869.
68. Hartikka J. Hefti F. Development of septal cholinergic neurons in culture: plating density and glial cells modulate effects of NGF on survival, fiber growth, and expression of transmitter-specific enzymes. J Neurosci 1988;8:2967-2985.
69. Lewis ME, Neff NT, Contreras PC, et al. Insulin-like growth factor-I: potential for treatment of motor neuronal disorders. Exp Neurol 1993;124:73-88.
70. Neff NT, Prevette D, Houenou LJ. et al. Insulin-like growth factors: putative muscle-derived trophic agents that promote motoneuron survival. J Neurobiol 1993;24:1578-1588.
71. Maroney AC, Glicksman MA, Basma AN, et al. Motoneuron apoptosis is blocked by CEP- 1347 (KT 7515), a novel inhibitor of the JNK signaling pathway. J Neurosci 1998;18:104-111.
72. Maroney AC, Finn JP, Bozyczko-Coyne D, et al. CEP-1347 (KT7515), an inhibitor of JNK activation, rescues sympathetic neurons and neuronally differentiated PC12 cells from death evoked by three distinct insults. J Neurochem 1999;73:1901-1912.
73. Saporito MS, Hudkins RL, Maroney AC. Discovery of CEP-1347/KT-7515, an inhibitor of the JNK/SAPK pathway for the treatment of neurodegenerative diseases. Prog Med Chem 2002;40:23-62.
74. Mathiasen JR, McKenna BA, Saporito MS, et al. Inhibition of mixed lineage kinase 3 attenuates MPP(+)-induced neurotoxicity in SH-SY5Y cells. Brain Res 2004;1003:86-97.
75. Takahashi T, Deng Y, Maruyama W, Dostert P, Kawai M, Naoi M. Uptake of a neurotoxin-candidate, (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline into human dopaminergic neuroblastoma SH-SY5Y cells by dopamine transport system. J Neural Transm Gen Sect 1994;98:107-118.
76. Farooqui SM. Induction of adenylate cyclase sensitive dopamine D2-receptors in retinoic acid induced differentiated human neuroblastoma SHSY-5Y cells. Life Sci 1994;55:1887-1893.
77. Jenkins R, Hunt SF. Long-term increase in the levels of c-jun mRNA and jun protein-like immunoreactivity in motor and sensory neurons following axon damage. Neurosci Lett 1991;129: 107-110.
78. Haas CA, Deller T, Naumann T, Frotscher M. Selective expression of the immediate early gene c-jun in axotomized rat medial septal neurons is not related to neuronal degeneration. J Neurosci 1996; 16:1894-1903.
79. Dragunow M, Young D, Hughes P, et al. Is c-Jun involved in nerve cell death following status epilepticus and hypoxic-ischaemic brain injury? Mol Brain Res 1993;18:347-352.
80. Gubits RM, Burke RE, Casey McIntosh G, Bandele A, Munell F. Immediate early gene induction after neonatal hypoxia-ischemia. Brain Res Mol Brain Res 1993;18:228-238.
81. Wessel TC, Joh TH, Volpe BT. In situ hybridization analysis of c-fos and c-jun expression in the rat brain following transient forebrain ischemia. Brain Res 1991;567:231-240.
82. Dragunow M, Beilharz E, Sirimanne E, et al. Immediate-early gene protein expression in neurons undergoing delayed death, but not necrosis, following hypoxic-ischaemic injury to the young rat brain. Mol Brain Res 1994;25:19-33.
83. Jenkins R, O'Shea R, Thomas KL, Hunt SP. c-jun expression in substantia nigra neurons following striatal 6-hydroxydopamine lesions in the rat. Neuroscience 1993;53:447-455.
84. Leah JD, Herdegen T, Murashov A, Dragunow M, Bravo R. Expression of immediate early gene proteins following axotomy and inhibition of axonal transport in the rat central nervous system. Neuroscience 1993;57:53-66.
85. Sauer H, Oertel WH. Progressive degeneration of nigrostriatal dopamine neurons following intrastriatal terminal lesions with 6 hydroxydopamine a combined retrograde tracing and immunocytochemical study in the rat. Neuroscience 1994;59:401-415.
86. Kerr JFR, Gobe GC, Winterford CM, Harmon BV. Anatomical methods in cell death. In: Schwartz LM, Osborne BA, editors. Methods in cell biology: cell death. New York: Academic Press: 1995. p 1-27.
87. Messina A, Jaworowski A, Bell C. Detection of jun but not fos protein during developmental cell death in sympathetic neurons. J Comp Neurol 1996;372:544-550.
88. Ferrer I, Olive M, Ribera J, Planas AM. Naturally occurring (programmed) and radiation-induced apoptosis are associated with selective c-jun expression in the developing rat brain. Eur J Neurosci 1996;8:1286-1298.
89. Ferrer I, Olive M, Blanco R, Cinos C, Planas AM. Selective c-Jun overexpression is associated with ionizing radiation-induced apoptosis in the developing cerebellum of the rat. Mol Brain Res 1996;38:91-100.
90. Herdegen T, Claret FX, Kallunki T, et al. Lasting N-terminal phosphorylation of c-Jun and activation of c-Jun N- terminal kinases after neuronal injury. J Neurosci 1998;18:5124-5135.
91. Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 1992;119:493-501.
92. Oo TF, Henchcliffe C, James D, Burke RE. Expression of c-fos, c-jun, and c-jun N-terminal kinase (JNK) in a developmental model of induced apoptotic death in neurons of the substantia nigra. J Neurochem 1999;72:557-564.
93. Yang DD, Kuan CY, Whitmarsh AJ, et al. Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 1997;389:865-870.
94. Crocker SJ, Lamba WR, Smith PD, et al. c-Jun mediates axotomy-induced dopamine neuron death in vivo. Proc Natl Acad Sci U S A 2001;98:13385-13390.
95. Teismann P, Tieu K, Choi DK, et al. Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc Natl Acad Sci U S A 2003;100:5473-5478.
96. Jackson-Lewis V, Jakowec M, Burke RE, Przedborski S. Time course and morphology of dopaminergic neuronal death caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine. Neurodegeneration 1995;4:257-269.
97. Furuya T, Hayakawa H, Yamada M, et al. Caspase-11 mediates inflammatory dopaminergic cell death in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. J Neurosci 2004;24:1865-1872.
98. Xu X, Raber J, Yang D, Su B, Mucke L. Dynamic regulation of c-Jun N-terminal kinase activity in mouse brain by environmental stimuli. Proc Natl Acad Sci U S A 1997;94:12655-12660.
99. Kuan CY, Yang DD, Samanta RD, Davis RJ, Rakic P, Flavell RA. The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron 1999;22: 667-676.
100. Murakata C, Kaneko M, Gessner G, et al. Mixed lineage kinase activity of indolocarbazole analogues. Bioorg Med Chem Lett 2002;12:147-150.
101. Glicksman MA, Chiu AY, Dionne CA, et al. CEP-1347/KT7515 prevents motor neuronal programmed cell death and injury-induced dedifferentiation in vivo. J Neurobiol 1998;35:361-370.
102. Saporito MS, Brown ER, Carswell S, et al. Preservation of cholinergic activity and prevention of neuron death by CEP-1347/KT-7515 following excitotoxic injury of the nucleus basalis magnocellularis. Neuroscience 1998;86:461-472.
103. Pirvola U, Xing-Qun L, Virkkala J, et al. Rescue of hearing, auditory hair cells, and neurons by CEP-1347/KT7515, an inhibitor of c-Jun N-terminal kinase activation. J Neurosci 2000;20: 43-50.
104. Saporito MS, Brown EM, Miller MS, Carswell S. CEP-1347/KT7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the 1-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons In vivo. J Pharmacol Exp Ther 1999;288:421-427.
105. Saporito MS, Thomas BA, Scott RW. MPTP activates c-Jun NH(2)-terminal kinase (JNK) and its upstream regulatory kinase MKK4 in nigrostriatal neurons in vivo. J Neurochem 2000;75: 1200-1208.
106. Anderson AJ, Cummings BJ, Cotman CW. Increased immunoreactivity for Jun- and Fos-related proteins in Alzheimer's disease: association with pathology. Exp Neurol 1994;125:286-295.
107. Anderson AJ, Su JH, Cotman CW. DNA damage and apoptosis in Alzheimer's disease: colocalization with c-Jun immunoreactivity, relationship to brain area, and effect of postmortem delay. J Neurosci 1996;16:1710-1719.
108. MacGibbon GA, Lawlor PA, Walton M, et al. Expression of Fos, Jun, and Krox family proteins in Alzheimer's disease. Exp Neurol 1997;147:316-332.
109. Marcus DL, Strafaci JA, Miller DC, et al. Quantitative neuronal c-fos and c-jun expression in Alzheimer's disease. Neurobiol Aging 1998;19:393-400.
110. Ferrer I, Blanco R, Carmona M, et al. Active, phosphorylation-dependent mitogen-activated protein kinase (MAPK/ERK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38 kinase expression in Parkinson's disease and Dementia with Lewy bodies. J Neural Transm 2001;108:1383-1396.
111. Jellinger KA. Cell death mechanisms in Parkinson's disease. J Neural Transm 2000;107:1-29.
112. Roux PP, Dorval G, Boudreau M, et al. K252a and CEP1347 are neuroprotective compounds that inhibit mixed-lineage kinase-3 and induce activation of Akt and ERK. J Biol Chem 2002;277: 49473-49480.