User menu

PKR, the double stranded RNA-dependent protein kinase as a critical target in Alzheimer's disease.

Bibliographic reference Morel, Milena ; Couturier, Julien ; Lafay-Chebassier, Claire ; Paccalin, Marc ; Page, Guylène. PKR, the double stranded RNA-dependent protein kinase as a critical target in Alzheimer's disease.. In: Journal of Cellular and Molecular Medicine : a journal of translational medicine, Vol. 13, no. 8A, p. 1476-1488 (2009)
Permanent URL
  1. Lage, J Alzheimers Dis., 9, 15 (2006)
  2. Saunders A.M, Roses A.D, Pericak-Vance M.A, Dole K.C, Strittmatter W.J, Schmechel D.E, Szymanski M.H, McCown N, Manwaring M.G, Schmader K, Breitner J.C.S, Goldgaber D, Benson M.D, Goldfarb L, Brown W.T, Apolipoprotein E ∈4 allele distributions in late-onset Alzheimer's disease and in other amyloid-forming diseases, 10.1016/0140-6736(93)91709-u
  3. Corder E., Saunders A., Strittmatter W., Schmechel D., Gaskell P., Small G., Roses A., Haines J., Pericak-Vance M., Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families, 10.1126/science.8346443
  4. Strittmatter W. J., Saunders A. M., Goedert M., Weisgraber K. H., Dong L. M., Jakes R., Huang D. Y., Pericak-Vance M., Schmechel D., Roses A. D., Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease., 10.1073/pnas.91.23.11183
  5. Huang David Y., Goedert Michel, Jakes Ross, Weisgraber Karl H., Garner Craig C., Saunders Ann M., Pericak-Vance Margaret A., Schmechel Donald E., Roses Allen D., Strittmatter Warren J., Isoform-specific interactions of apolipoprotein E with the microtubule-associated protein MAP2c: implications for Alzheimer's disease, 10.1016/0304-3940(94)90204-6
  6. Poirier, J Neural Transm Suppl., 53, 199 (1998)
  7. Rogaeva Ekaterina, Meng Yan, Lee Joseph H, Gu Yongjun, Kawarai Toshitaka, Zou Fanggeng, Katayama Taiichi, Baldwin Clinton T, Cheng Rong, Hasegawa Hiroshi, Chen Fusheng, Shibata Nobuto, Lunetta Kathryn L, Pardossi-Piquard Raphaelle, Bohm Christopher, Wakutani Yosuke, Cupples L Adrienne, Cuenco Karen T, Green Robert C, Pinessi Lorenzo, Rainero Innocenzo, Sorbi Sandro, Bruni Amalia, Duara Ranjan, Friedland Robert P, Inzelberg Rivka, Hampe Wolfgang, Bujo Hideaki, Song You-Qiang, Andersen Olav M, Willnow Thomas E, Graff-Radford Neill, Petersen Ronald C, Dickson Dennis, Der Sandy D, Fraser Paul E, Schmitt-Ulms Gerold, Younkin Steven, Mayeux Richard, Farrer Lindsay A, St George-Hyslop Peter, The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease, 10.1038/ng1943
  8. Lee Joseph H., Cheng Rong, Schupf Nicole, Manly Jennifer, Lantigua Rafael, Stern Yaakov, Rogaeva Ekaterina, Wakutani Yosuke, Farrer Lindsay, St. George-Hyslop Peter, Mayeux Richard, The Association Between Genetic Variants in SORL1 and Alzheimer Disease in an Urban, Multiethnic, Community-Based Cohort, 10.1001/archneur.64.4.501
  9. Lichtenthaler S. F., Wang R., Grimm H., Uljon S. N., Masters C. L., Beyreuther K., Mechanism of the cleavage specificity of Alzheimer's disease  -secretase identified by phenylalanine-scanning mutagenesis of the transmembrane domain of the amyloid precursor protein, 10.1073/pnas.96.6.3053
  10. Vassar Robert, Citron Martin, Aβ-Generating Enzymes, 10.1016/s0896-6273(00)00051-9
  11. Hardy J., Higgins G., Alzheimer's disease: the amyloid cascade hypothesis, 10.1126/science.1566067
  12. KIDD M., Paired Helical Filaments in Electron Microscopy of Alzheimer's Disease, 10.1038/197192b0
  13. Goedert, J Alzheimers Dis., 9, 195 (2006)
  14. Fischer Oskar, Die presbyophrene demenz, deren anatomische grundlage und klinische Abgrenzung, 10.1007/bf02893605
  15. HENEKA M, OBANION M, Inflammatory processes in Alzheimer's disease, 10.1016/j.jneuroim.2006.11.017
  16. BONIFATI D, KISHORE U, Role of complement in neurodegeneration and neuroinflammation, 10.1016/j.molimm.2006.03.007
  17. ITAGAKI S, MCGEER P, AKIYAMA H, ZHU S, SELKOE D, Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease, 10.1016/0165-5728(89)90115-x
  18. Rozemuller J.M., Eikelenboom P., Pals S.T., Stam F.C., Microglial cells around amyloid plaques in Alzheimer's disease express leucocyte adhesion molecules of the LFA-1 family, 10.1016/0304-3940(89)90547-8
  19. McGeer, J Alzheimers Dis., 9, 271 (2006)
  20. McGEER P. L., Inflammation and the Degenerative Diseases of Aging, 10.1196/annals.1332.007
  21. Webster S, Lue L.-F, Brachova L, Tenner A.J, McGeer P.L, Terai K, Walker D.G, Bradt B, Cooper N.R, Rogers J, Molecular and Cellular Characterization of the Membrane Attack Complex, C5b-9, in Alzheimer’s Disease, 10.1016/s0197-4580(97)00042-0
  22. McGeer P.L., Akiyama H., Itagaki S., McGeer E.G., Activation of the classical complement pathway in brain tissue of Alzheimer patients, 10.1016/0304-3940(89)90843-4
  23. Davies, J Alzheimers Dis., 9, 265 (2006)
  24. Nixon, J Alzheimers Dis., 9, 277 (2006)
  25. van Leeuwen, J Alzheimers Dis., 9, 319 (2006)
  26. Smith, J Alzheimers Dis., 9, 305 (2006)
  27. Lafay-Chebassier Claire, Paccalin Marc, Page Guylene, Barc-Pain Stephanie, Perault-Pochat Marie Christine, Gil Roger, Pradier Laurent, Hugon Jacques, mTOR/p70S6k signalling alteration by Abeta exposure as well as in APP-PS1 transgenic models and in patients with Alzheimer's disease, 10.1111/j.1471-4159.2005.03187.x
  28. Suen Ka-Chun, Yu Man-Shan, So Kwok-Fai, Chang Raymond Chuen-Chung, Hugon Jacques, Upstream Signaling Pathways Leading to the Activation of Double-stranded RNA-dependent Serine/Threonine Protein Kinase in β-Amyloid Peptide Neurotoxicity, 10.1074/jbc.m306503200
  29. Peel A, Activation of the cell stress kinase PKR in Alzheimer's disease and human amyloid precursor protein transgenic mice, 10.1016/s0969-9961(03)00086-x
  30. Chang Raymond Chuen-Chung, Suen Ka-Chun, Ma Chi-Him, Elyaman Wassim, Ng Ho-Keung, Hugon Jacques, Involvement of double-stranded RNA-dependent protein kinase and phosphorylation of eukaryotic initiation factor-2α in neuronal degeneration : PKR and eIF2α in neurodegeneration, 10.1046/j.1471-4159.2002.01237.x
  31. Sonenberg Nahum, Hinnebusch Alan G., Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets, 10.1016/j.cell.2009.01.042
  32. Pain Virginia M., Initiation of Protein Synthesis in Eukaryotic Cells, 10.1111/j.1432-1033.1996.00747.x
  33. Pain V M, Initiation of protein synthesis in mammalian cells, 10.1042/bj2350625
  34. Merrick, Microbiol Rev., 56, 291 (1992)
  35. Fekete Christie A, Mitchell Sarah F, Cherkasova Vera A, Applefield Drew, Algire Mikkel A, Maag David, Saini Adesh K, Lorsch Jon R, Hinnebusch Alan G, N- and C-terminal residues of eIF1A have opposing effects on the fidelity of start codon selection, 10.1038/sj.emboj.7601613
  36. Pestova, In translational control in biology and medicine, 87 (2007)
  37. Hinnebusch, In translational control in biology and medicine, 225 (2007)
  38. Chatterjee Sangeeta, Pal Jayanta K., Role of 5′- and 3′-untranslated regions of mRNAs in human diseases, 10.1042/bc20080104
  39. Cazzola, Blood., 95, 3280 (2000)
  40. Zhou W., Song W., Leaky Scanning and Reinitiation Regulate BACE1 Gene Expression, 10.1128/mcb.26.9.3353-3364.2006
  41. Niesler Beate, Kapeller Johannes, Hammer Christian, Rappold Gudrun, Serotonin type 3 receptor genes:HTR3A, B, C, D, E, 10.2217/14622416.9.5.501
  42. Soifer Harris S, Rossi John J, Sætrom Pål, MicroRNAs in Disease and Potential Therapeutic Applications, 10.1038/
  43. Conne Béatrice, Stutz André, Vassalli Jean-Dominique, 10.1038/76211
  44. Williams Bryan RG, PKR; a sentinel kinase for cellular stress, 10.1038/sj.onc.1203127
  45. Dever Thomas E., Feng Lan, Wek Ronald C., Cigan A.Mark, Donahue Thomas F., Hinnebusch Alan G., Phosphorylation of initiation factor 2α by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast, 10.1016/0092-8674(92)90193-g
  46. Ron, In translational control in biology and medicine, 345 (2007)
  47. Ladiges Warren, Morton John, Blakely Collin, Gale Michael, Tissue specific expression of PKR protein kinase in aging B6D2F1 mice, 10.1016/s0047-6374(00)00097-x
  48. Peel A. L., Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to Huntington's disease (HD) transcripts and is activated in HD tissue, 10.1093/hmg/10.15.1531
  49. BANDO Y, ONUKI R, KATAYAMA T, MANABE T, KUDO T, TAIRA K, TOHYAMA M, Double-strand RNA dependent protein kinase (PKR) is involved in the extrastriatal degeneration in Parkinson's disease and Huntington's disease, 10.1016/j.neuint.2004.07.005
  50. Chang Raymond C. C., Wong Ada K. Y., Ng Ho-Keung, Hugon Jacques, Phosphorylation of eukaryotic initiation factor-2α (eIF2α) is associated with neuronal degeneration in Alzheimerʼs disease : , 10.1097/00001756-200212200-00011
  51. Frerichs K. U., Smith C. B., Brenner M., DeGracia D. J., Krause G. S., Marrone L., Dever T. E., Hallenbeck J. M., Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation, 10.1073/pnas.95.24.14511
  52. Alirezaei Mehrdad, Nairn Angus C., Glowinski Jacques, Prémont Joël, Marin Philippe, Zinc Inhibits Protein Synthesis in Neurons : POTENTIAL ROLE OF PHOSPHORYLATION OF TRANSLATION INITIATION FACTOR-2α, 10.1074/jbc.274.45.32433
  53. DeGracia Donald J., Adamczyk Steven, Folbe Adam J., Konkoly Lynette L., Pittman Joel E., Neumar Robert W., Sullivan Jonathon M., Scheuner Donalyn, Kaufman Randal J., White Blaine C., Krause Gary S., Eukaryotic Initiation Factor 2α Kinase and Phosphatase Activity during Postischemic Brain Reperfusion, 10.1006/exnr.1998.6986
  54. Welsh Gavin I, Miller Christa M, Loughlin A.Jane, Price Nigel T, Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin, 10.1016/s0014-5793(97)01548-2
  55. Takashima, J Alzheimers Dis., 9, 309 (2006)
  56. Romano, Mol Cell Biol., 18, 2282 (1998)
  57. Bennett R. L., RAX, the PKR activator, sensitizes cells to inflammatory cytokines, serum withdrawal, chemotherapy, and viral infection, 10.1182/blood-2005-11-006817
  58. Patel R. C., PACT, a protein activator of the interferon-induced protein kinase, PKR, 10.1093/emboj/17.15.4379
  59. Clemens M.J., Translational regulation in cell stress and apoptosis. Roles of the eIF4E binding proteins, 10.1111/j.1582-4934.2001.tb00157.x
  60. CLEMENS MICHAEL J., ELIA ANDROULLA, The Double-Stranded RNA-Dependent Protein Kinase PKR: Structure and Function, 10.1089/jir.1997.17.503
  61. Balachandran, Methods Mol Biol., 383, 277 (2007)
  62. Der S. D., Yang Y.-L., Weissmann C., Williams B. R. G., A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis, 10.1073/pnas.94.7.3279
  63. Srivastava Sri P., Kumar Kotlo U., Kaufman Randal J., Phosphorylation of Eukaryotic Translation Initiation Factor 2 Mediates Apoptosis in Response to Activation of the Double-stranded RNA-dependent Protein Kinase, 10.1074/jbc.273.4.2416
  64. Cuddihy Andrew R, Hoi-Tao Wong Andrew, Wai Ning Tam Nancy, Li Suiyang, Koromilas Antonis E, The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro, 10.1038/sj.onc.1202620
  65. Gil Jesús, Esteban Mariano, 10.1023/a:1009664109241
  66. Goh K. C., The protein kinase PKR is required for p38 MAPK activation and the innate immune response to bacterial endotoxin, 10.1093/emboj/19.16.4292
  67. Balachandran Siddharth, Kim Caryn N., Yeh Wen-Chen, Mak Tak W., Bhalla Kapil, Barber Glen N., Activation of the dsRNA-dependent protein kinase, PKR, induces apoptosis through FADD-mediated death signaling, 10.1093/emboj/17.23.6888
  68. Ramana Chilakamarti V., Grammatikakis Nicholas, Chernov Mikhail, Nguyen Hannah, Chuan Goh Kee, Williams Bryan R.G., Stark George R., Regulation of c-myc expression by IFN-γ through Stat1-dependent and -independent pathways, 10.1093/emboj/19.2.263
  69. Guerra Susana, López-Fernández Luis A., García María Angel, Zaballos Angel, Esteban Mariano, Human Gene Profiling in Response to the Active Protein Kinase, Interferon-induced Serine/threonine Protein Kinase (PKR), in Infected Cells : INVOLVEMENT OF THE TRANSCRIPTION FACTOR ATF-3 IN PKR-INDUCED APOPTOSIS, 10.1074/jbc.m511983200
  70. Raught, In translational control in biology and medicine, 369 (2007)
  71. Raught B., Gingras A.-C., Sonenberg N., The target of rapamycin (TOR) proteins, 10.1073/pnas.121145898
  72. Schmelzle Tobias, Hall Michael N, TOR, a Central Controller of Cell Growth, 10.1016/s0092-8674(00)00117-3
  73. Bhaskar Prashanth T., Hay Nissim, The Two TORCs and Akt, 10.1016/j.devcel.2007.03.020
  74. De Virgilio Claudio, Loewith Robbie, The TOR signalling network from yeast to man, 10.1016/j.biocel.2006.02.013
  75. Ma Xiaoju Max, Blenis John, Molecular mechanisms of mTOR-mediated translational control, 10.1038/nrm2672
  76. Holz Marina K., Ballif Bryan A., Gygi Steven P., Blenis John, mTOR and S6K1 Mediate Assembly of the Translation Preinitiation Complex through Dynamic Protein Interchange and Ordered Phosphorylation Events, 10.1016/j.cell.2005.10.024
  77. Dufner Almut, Thomas George, Ribosomal S6 Kinase Signaling and the Control of Translation, 10.1006/excr.1999.4683
  78. Krymskaya, Cell Signal., 15, 729 (2003)
  79. Long Xiaomeng, Lin Yenshou, Ortiz-Vega Sara, Yonezawa Kazuyoshi, Avruch Joseph, Rheb Binds and Regulates the mTOR Kinase, 10.1016/j.cub.2005.02.053
  80. Manning B, Rheb fills a GAP between TSC and TOR, 10.1016/j.tibs.2003.09.003
  81. Luo Hongyu, Duguid William, Chen Huifang, Maheu Michel, Wu Jiangping, The effect of rapamycin on T cell development in mice, 10.1002/eji.1830240331
  82. Ruvolo Vivian R., Kurinna Svitlana M., Karanjeet Kul B., Schuster Todd F., Martelli Alberto M., McCubrey James A., Ruvolo Peter P., PKR Regulates B56α-mediated BCL2 Phosphatase Activity in Acute Lymphoblastic Leukemia-derived REH Cells, 10.1074/jbc.m800951200
  83. Jeffrey, Cancer Res., 62, 2272 (2002)
  84. Xu Z., Williams B. R. G., The B56alpha Regulatory Subunit of Protein Phosphatase 2A Is a Target for Regulation by Double-Stranded RNA-Dependent Protein Kinase PKR, 10.1128/mcb.20.14.5285-5299.2000
  85. Tang S. J., Reis G., Kang H., Gingras A.-C., Sonenberg N., Schuman E. M., A rapamycin-sensitive signaling pathway contributes to long-term synaptic plasticity in the hippocampus, 10.1073/pnas.012605299
  86. Nguyen Peter V, Protein synthesis during LTP: linking synaptic activity to translation, 10.1016/s0166-2236(02)02166-5
  87. Langstrom N.S., Anderson J.P., Lindroos H.G., Winbland B., Wallace W.C., Alzheimer's disease-associated reduction of polysomal mRNA translation, 10.1016/0169-328x(89)90060-0
  88. Johnson Ginger, Gotlib Jason, Haroutunian Vahram, Bierer Linda, Nairn Angus C., Merril Carl, Wallace William, Increased phosphorylation of elongation factor 2 in Alzheimer's disease, 10.1016/0169-328x(92)90124-t
  89. Lafay-Chebassier Claire, Pérault-Pochat Marie Christine, Page Guylène, Bilan Agnès Rioux, Damjanac Milena, Pain Stéphanie, Houeto Jean-Luc, Gil Roger, Hugon Jacques, The immunosuppressant rapamycin exacerbates neurotoxicity of Aβ peptide, 10.1002/jnr.21039
  90. Casas, Am J Pathol., 165, 1289 (2004)
  91. Damjanac Milena, Rioux Bilan Agnès, Paccalin Marc, Pontcharraud Raymond, Fauconneau Bernard, Hugon Jacques, Page Guylène, Dissociation of Akt/PKB and ribosomal S6 kinase signaling markers in a transgenic mouse model of Alzheimer’s disease, 10.1016/j.nbd.2007.09.008
  92. Li Xu, Alafuzoff Irina, Soininen Hilkka, Winblad Bengt, Pei Jin-Jing, Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain : Abnormal translation control in Alzheimer's disease, 10.1111/j.1742-4658.2005.04833.x
  93. Li Xu, An Wen-Lin, Alafuzoff Irina, Soininen Hilkka, Winblad Bengt, Pei Jin-Jing, Phosphorylated eukaryotic translation factor 4E is elevated in Alzheimer brain : , 10.1097/00001756-200410050-00019
  94. Pei Jin-Jing, Hugon Jacques, mTOR-dependent signalling in Alzheimer's disease, 10.1111/j.1582-4934.2008.00509.x
  95. Onuki Reiko, Bando Yoshio, Suyama Eigo, Katayama Taiichi, Kawasaki Hiroaki, Baba Tadashi, Tohyama Masaya, Taira Kazunari, An RNA-dependent protein kinase is involved in tunicamycin-induced apoptosis and Alzheimer's disease, 10.1038/sj.emboj.7600049
  96. Peel, J Neuropathol Exp Neurol., 63, 97 (2004)
  97. Page G., Rioux Bilan A., Ingrand S., Lafay-Chebassier C., Pain S., Perault Pochat M.C., Bouras C., Bayer T., Hugon J., Activated double-stranded RNA-dependent protein kinase and neuronal death in models of Alzheimer’s disease, 10.1016/j.neuroscience.2006.01.047
  98. Damjanac Milena, Bilan Agnès Rioux, Barrier Laurence, Pontcharraud Raymond, Anne Cantereau, Hugon Jacques, Page Guylène, Fluoro-Jade® B staining as useful tool to identify activated microglia and astrocytes in a mouse transgenic model of Alzheimer's disease, 10.1016/j.brainres.2006.05.050
  99. Eikelenboom P., Veerhuis R., Scheper W., Rozemuller A. J. M., van Gool W. A., Hoozemans J. J. M., The significance of neuroinflammation in understanding Alzheimer’s disease, 10.1007/s00702-006-0575-6
  100. Hoozemans Jeroen J.M, Veerhuis Robert, Rozemuller Annemieke J.M, Arendt Thomas, Eikelenboom Piet, Neuronal COX-2 expression and phosphorylation of pRb precede p38 MAPK activation and neurofibrillary changes in AD temporal cortex, 10.1016/j.nbd.2003.11.028
  101. Paccalin Marc, Pain-Barc Stéphanie, Pluchon Claudette, Paul Chloé, Besson Marie-Noelle, Carret-Rebillat Anne-Sophie, Rioux-Bilan Agnès, Gil Roger, Hugon Jacques, Activated mTOR and PKR Kinases in Lymphocytes Correlate with Memory and Cognitive Decline in Alzheimer’s Disease, 10.1159/000095562
  102. Damjanac Milena, Page Guylène, Ragot Stéphanie, Laborie Guillaume, Gil Roger, Hugon Jacques, Paccalin Marc, PKR, a cognitive decline biomarker, can regulate translationviatwo consecutive molecular targets p53 and Redd1 in lymphocytes of AD patients, 10.1111/j.1582-4934.2009.00688.x
  103. Feng Z., Hu W., de Stanchina E., Teresky A. K., Jin S., Lowe S., Levine A. J., The Regulation of AMPK  1, TSC2, and PTEN Expression by p53: Stress, Cell and Tissue Specificity, and the Role of These Gene Products in Modulating the IGF-1-AKT-mTOR Pathways, 10.1158/0008-5472.can-06-4149
  104. Levine A. J., Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways, 10.1101/gad.1363206
  105. Feng Z., Zhang H., Levine A. J., Jin S., The coordinate regulation of the p53 and mTOR pathways in cells, 10.1073/pnas.0502857102
  106. Ellisen Leif W, Ramsayer Kate D, Johannessen Cory M, Yang Annie, Beppu Hideyuki, Minda Karolina, Oliner Jonathan D, McKeon Frank, Haber Daniel A, REDD1, a Developmentally Regulated Transcriptional Target of p63 and p53, Links p63 to Regulation of Reactive Oxygen Species, 10.1016/s1097-2765(02)00706-2
  107. Jin Hyeon-Ok, An Sungkwan, Lee Hyung-Chahn, Woo Sang-Hyeok, Seo Sung-Keum, Choe Tae-Boo, Yoo Doo-Hyun, Lee Seung-Bum, Um Hong-Duck, Lee Su-Jae, Hypoxic condition- and high cell density-induced expression of Redd1 is regulated by activation of hypoxia-inducible factor-1α and Sp1 through the phosphatidylinositol 3-kinase/Akt signaling pathway, 10.1016/j.cellsig.2006.12.014
  108. Brugarolas J., Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex, 10.1101/gad.1256804
  109. Corradetti Michael N., Inoki Ken, Guan Kun-Liang, The Stress-inducted Proteins RTP801 and RTP801L Are Negative Regulators of the Mammalian Target of Rapamycin Pathway, 10.1074/jbc.c400557200
  110. Shoshani T., Faerman A., Mett I., Zelin E., Tenne T., Gorodin S., Moshel Y., Elbaz S., Budanov A., Chajut A., Kalinski H., Kamer I., Rozen A., Mor O., Keshet E., Leshkowitz D., Einat P., Skaliter R., Feinstein E., Identification of a Novel Hypoxia-Inducible Factor 1-Responsive Gene, RTP801, Involved in Apoptosis, 10.1128/mcb.22.7.2283-2293.2002
  111. Sofer A., Lei K., Johannessen C. M., Ellisen L. W., Regulation of mTOR and Cell Growth in Response to Energy Stress by REDD1, 10.1128/mcb.25.14.5834-5845.2005
  112. Ellisen, Cell Cycle., 4, 1500 (2005)
  113. Jozwiak Jaroslaw, Jozwiak Sergiusz, Grzela Tomasz, Lazarczyk Maciej, Positive and Negative Regulation of TSC2 Activity and Its Effects on Downstream Effectors of the mTOR Pathway, 10.1385/nmm:7:4:287
  114. Kimball Scot R., Do A. N. Dang, Kutzler Lydia, Cavener Douglas R., Jefferson Leonard S., Rapid Turnover of the mTOR Complex 1 (mTORC1) Repressor REDD1 and Activation of mTORC1 Signaling following Inhibition of Protein Synthesis, 10.1074/jbc.m706643200
  115. Wang Hongmei, Kubica Neil, Ellisen Leif W., Jefferson Leonard S., Kimball Scot R., Dexamethasone Represses Signaling through the Mammalian Target of Rapamycin in Muscle Cells by Enhancing Expression of REDD1, 10.1074/jbc.m610023200
  116. Lanni, Mol Psychiatry., 13, 641 (2008)
  117. Uberti Daniela, Lanni Cristina, Carsana Teresina, Francisconi Simona, Missale Cristina, Racchi Marco, Govoni Stefano, Memo Maurizio, Identification of a mutant-like conformation of p53 in fibroblasts from sporadic Alzheimer's disease patients, 10.1016/j.neurobiolaging.2005.06.013
  118. Lanni, J Alzheimers Dis., 12, 93 (2007)
  119. Uberti, J Neurochem., 103, 322 (2007)
  120. Uberti, J Cell Sci., 115, 3131 (2002)
  121. Baltzis Dionissios, Pluquet Olivier, Papadakis Andreas I., Kazemi Shirin, Qu Li-Ke, Koromilas Antonis E., The eIF2α Kinases PERK and PKR Activate Glycogen Synthase Kinase 3 to Promote the Proteasomal Degradation of p53, 10.1074/jbc.m704491200
  122. Marques J. T., Rebouillat D., Ramana C. V., Murakami J., Hill J. E., Gudkov A., Silverman R. H., Stark G. R., Williams B. R. G., Down-Regulation of p53 by Double-Stranded RNA Modulates the Antiviral Response, 10.1128/jvi.79.17.11105-11114.2005
  123. Opferman J T, Zambetti G P, Translational research? Ribosome integrity and a new p53 tumor suppressor checkpoint, 10.1038/sj.cdd.4401923
  124. Paccalin Marc, Khidir Fuad Al, Barc Stéphanie Pain, Pluchon Claudette, Perrault-Pochat Marie-Christine, Gil Roger, Hugon Jacques, Peripheral p70S6k levels and emotional memory in patients with Alzheimer's disease, 10.1016/j.neulet.2006.07.053
  125. Rosner Margit, Hanneder Michaela, Siegel Nicol, Valli Alessandro, Hengstschläger Markus, The tuberous sclerosis gene products hamartin and tuberin are multifunctional proteins with a wide spectrum of interacting partners, 10.1016/j.mrrev.2008.01.001
  126. Shumway Stuart D., Li Yong, Xiong Yue, 14-3-3β Binds to and Negatively Regulates the Tuberous Sclerosis Complex 2 (TSC2) Tumor Suppressor Gene Product, Tuberin, 10.1074/jbc.c200499200
  127. DeYoung M. P., Horak P., Sofer A., Sgroi D., Ellisen L. W., Hypoxia regulates TSC1/2 mTOR signaling and tumor suppression through REDD1-mediated 14 3 3 shuttling, 10.1101/gad.1617608
  128. Kim, Exp Mol Med., 35, 403 (2003)
  129. Morel Milena, Couturier Julien, Pontcharraud Raymond, Gil Roger, Fauconneau Bernard, Paccalin Marc, Page Guylène, Evidence of molecular links between PKR and mTOR signalling pathways in Aβ neurotoxicity: Role of p53, Redd1 and TSC2, 10.1016/j.nbd.2009.07.004
  130. Liu David X., Greene Lloyd A., Neuronal apoptosis at the G1/S cell cycle checkpoint, 10.1007/s004410100396
  131. Nagy Z, Cell cycle regulatory failure in neurones: causes and consequences, 10.1016/s0197-4580(00)00223-2
  132. Neve Rachael L., McPhie Donna L., The cell cycle as a therapeutic target for Alzheimer's disease, 10.1016/j.pharmthera.2005.09.005
  133. Busser, J Neurosci., 18, 2801 (1998)
  134. McShea, Am J Pathol., 150, 1933 (1997)
  135. Nagy Zsuzsanna, The last neuronal division: a unifying hypothesis for the pathogenesis of Alzheimer's disease, 10.1111/j.1582-4934.2005.tb00485.x
  136. Nagy Z., Esiri M. M., Smith A. D., Expression of cell division markers in the hippocampus in Alzheimer's disease and other neurodegenerative conditions, 10.1007/s004010050617
  137. Vincent I., Mitotic mechanisms in Alzheimer's disease?, 10.1083/jcb.132.3.413
  138. Raven Jennifer F., Baltzis Dionissios, Wang Shuo, Mounir Zineb, Papadakis Andreas I., Gao Hong Qing, Koromilas Antonis E., PKR and PKR-like Endoplasmic Reticulum Kinase Induce the Proteasome-dependent Degradation of Cyclin D1 via a Mechanism Requiring Eukaryotic Initiation Factor 2α Phosphorylation, 10.1074/jbc.m709677200
  139. Zacharek Sima J., Xiong Yue, Shumway Stuart D., Negative Regulation of TSC1-TSC2 by Mammalian D-Type Cyclins, 10.1158/0008-5472.can-05-2236
  140. Lanni C, Racchi M, Mazzini G, Ranzenigo A, Polotti R, Sinforiani E, Olivari L, Barcikowska M, Styczynska M, Kuznicki J, Szybinska A, Govoni S, Memo M, Uberti D, Conformationally altered p53: a novel Alzheimer's disease marker?, 10.1038/
  141. Tang Kun, Hynan Linda S., Baskin Fred, Rosenberg Roger N., Platelet amyloid precursor protein processing: A bio-marker for Alzheimer's disease, 10.1016/j.jns.2005.09.002
  142. Paccalin, Arch Intern Med., 165, 2428 (2005)
  143. Eckert Anne, Schindowski Katharina, Leutner Silke, Luckhaus Christian, Touchet Nathalie, Czech Christian, Müller Walter E., Alzheimer's Disease-like Alterations in Peripheral Cells from Presenilin-1 Transgenic Mice, 10.1006/nbdi.2000.0378
  144. Schindowski Katharina, Kratzsch Tilmann, Peters Jürgen, Steiner Barbara, Leutner Silke, Touchet Natalie, Maurer Konrad, Czech Christian, Pradier Laurent, Frölich Lutz, Müller Walter E., Eckert Anne, Impact of Aging: Sporadic, and Genetic Risk Factors on Vulnerability to Apoptosis in Alzheimer's Disease, 10.1385/nmm:4:3:161
  145. Ray Sandip, Britschgi Markus, Herbert Charles, Takeda-Uchimura Yoshiko, Boxer Adam, Blennow Kaj, Friedman Leah F, Galasko Douglas R, Jutel Marek, Karydas Anna, Kaye Jeffrey A, Leszek Jerzy, Miller Bruce L, Minthon Lennart, Quinn Joseph F, Rabinovici Gil D, Robinson William H, Sabbagh Marwan N, So Yuen T, Sparks D Larry, Tabaton Massimo, Tinklenberg Jared, Yesavage Jerome A, Tibshirani Robert, Wyss-Coray Tony, Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins, 10.1038/nm1653
  146. Lombardi V.R.M, Garcı́a M, Rey L, Cacabelos R, Characterization of cytokine production, screening of lymphocyte subset patterns and in vitro apoptosis in healthy and Alzheimer's Disease (AD) individuals, 10.1016/s0165-5728(99)00046-6
  147. Shalit F., Sredni B., Brodie C., Kott E., Huberman M., T Lymphocyte Subpopulations and Activation Markers Correlate with Severity of Alzheimer's Disease, 10.1006/clin.1995.1078
  148. Juntilla Marisa M., Koretzky Gary A., Critical roles of the PI3K/Akt signaling pathway in T cell development, 10.1016/j.imlet.2007.12.008
  149. Schmitz Frank, Heit Antje, Dreher Stefan, Eisenächer Katharina, Mages Jörg, Haas Tobias, Krug Anne, Janssen Klaus-Peter, Kirschning Carsten J., Wagner Hermann, Mammalian target of rapamycin (mTOR) orchestrates the defense program of innate immune cells, 10.1002/eji.200838761
  150. Wyss-Coray, Nat Med., 12, 1005 (2006)
  151. Wyss-Coray Tony, Mucke Lennart, Inflammation in Neurodegenerative Disease—A Double-Edged Sword, 10.1016/s0896-6273(02)00794-8
  152. Miscia Sebastiano, Ciccocioppo Fausta, Lanuti Paola, Velluto Lucia, Bascelli Adriana, Pierdomenico Laura, Genovesi Domenico, Di Siena Alessandro, Santavenere Eugenio, Gambi Francesco, Ausili-Cèfaro Giampiero, Grimley Philip M., Marchisio Marco, Gambi Domenico, Aβ1–42 stimulated T cells express P-PKC-δ and P-PKC-ζ in Alzheimer disease, 10.1016/j.neurobiolaging.2007.07.011
  153. Town Terrence, Tan Jun, Flavell Richard A., Mullan Mike, T-Cells in Alzheimer's Disease, 10.1385/nmm:7:3:255
  154. Huberman M., Sredni B., Stern L., Kott E., Shalit F., IL-2 and IL-6 secretion in dementia: correlation with type and severity of disease, 10.1016/0022-510x(95)00016-u
  155. Shalit F., Sredni B., Stern L., Kott E., Huberman M., Elevated interleukin-6 secretion levels by mononuclear cells of Alzheimer's patients, 10.1016/0304-3940(94)90003-5
  156. Gutierrez Enrique G., Banks William A., Kastin Abba J., Murine tumor necrosis factor alpha is transported from blood to brain in the mouse, 10.1016/0165-5728(93)90027-v
  157. Jiang Y., Deacon R., Anthony D.C., Campbell S.J., Inhibition of peripheral TNF can block the malaise associated with CNS inflammatory diseases, 10.1016/j.nbd.2008.06.017
  158. Itagaki S., McGeer P.L., Akiyama H., Presence of T-cytotoxic suppressor and leucocyte common antigen positive cells in Alzheimer's disease brain tissue, 10.1016/0304-3940(88)90690-8
  159. Rogers Joseph, Luber-Narod Judith, Styren Scot D., Civin W. Harold, Expression of immune system-associated antigens by cells of the human central nervous system: Relationship to the pathology of Alzheimer's disease, 10.1016/s0197-4580(88)80079-4
  160. Togo Takashi, Akiyama Haruhiko, Iseki Eizo, Kondo Hiromi, Ikeda Kenji, Kato Masanori, Oda Tatsuro, Tsuchiya Kuniaki, Kosaka Kenji, Occurrence of T cells in the brain of Alzheimer's disease and other neurological diseases, 10.1016/s0165-5728(01)00496-9
  161. Monsonego A., Imitola J., Zota V., Oida T., Weiner H. L., Microglia-Mediated Nitric Oxide Cytotoxicity of T Cells Following Amyloid  -Peptide Presentation to Th1 Cells, 10.4049/jimmunol.171.5.2216
  162. Monsonego Alon, Zota Victor, Karni Arnon, Krieger Jeffery I., Bar-Or Amit, Bitan Gal, Budson Andrew E., Sperling Reisa, Selkoe Dennis J., Weiner Howard L., Increased T cell reactivity to amyloid β protein in older humans and patients with Alzheimer disease, 10.1172/jci200318104
  163. Séguin Rosanne, Biernacki Katarzyna, Prat Alexandre, Wosik Karolina, Kim Ho-Jin, Blain Manon, Mccrea Ellie, Bar-Or Amit, Antel Jack P., Differential effects of Th1 and Th2 lymphocyte supernatants on human microglia : Th1 and Th2 Effects on Human Microglia, 10.1002/glia.10201
  164. Farfara D., Lifshitz V., Frenkel D., Neuroprotective and neurotoxic properties of glial cells in the pathogenesis of Alzheimer's disease, 10.1111/j.1582-4934.2008.00314.x
  165. Akiyama H, Inflammation and Alzheimer's disease, 10.1016/s0197-4580(00)00124-x
  166. Tan Jun, Town Terrence, Crawford Fiona, Mori Takashi, DelleDonne Anthony, Crescentini Robert, Obregon Demian, Flavell Richard A., Mullan Michael J., Role of CD40 ligand in amyloidosis in transgenic Alzheimer's mice, 10.1038/nn968
  167. Liu, Neurobiol Aging. (2008)
  168. Nagy Zsuzsanna, Combrinck Marc, Budge Marc, McShane Rupert, Cell cycle kinesis in lymphocytes in the diagnosis of Alzheimer's disease, 10.1016/s0304-3940(01)02442-9
  169. Stieler Jens T., Lederer Carla, Brückner Martina K., Wolf Henrike, Holzer Max, Gertz Hermann-Josef, Arendt Thomas, Impairment of mitogenic activation of peripheral blood lymphocytes in Alzheimer's disease : , 10.1097/00001756-200112210-00023
  170. Ryu, J Neurosci., 22, 10690 (2002)
  171. Garcia M. A., Gil J., Ventoso I., Guerra S., Domingo E., Rivas C., Esteban M., Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action, 10.1128/mmbr.00027-06
  172. Gern James E., French Delores A., Grindle Kristine A., Brockman-Schneider Rebecca A., Konno Shin-Ichi, Busse William W., Double-Stranded RNA Induces the Synthesis of Specific Chemokines by Bronchial Epithelial Cells, 10.1165/rcmb.2002-0055oc
  173. Matsukura Satoshi, Kokubu Fumio, Kurokawa Masatsugu, Kawaguchi Mio, Ieki Koushi, Kuga Hideki, Odaka Miho, Suzuki Shintaro, Watanabe Shin, Homma Tetsuya, Takeuchi Hiroko, Nohtomi Kyoko, Adachi Mitsuru, Role of RIG-I, MDA-5, and PKR on the Expression of Inflammatory Chemokines Induced by Synthetic dsRNA in Airway Epithelial Cells, 10.1159/000101411
  174. Gil, Mol Cell Biol., 19, 4653 (1999)
  175. Taddeo B., Luo T. R., Zhang W., Roizman B., Activation of NF- B in cells productively infected with HSV-1 depends on activated protein kinase R and plays no apparent role in blocking apoptosis, 10.1073/pnas.2034952100
  176. Bonnet Marion C., Daurat Caroline, Ottone Catherine, Meurs Eliane F., The N-terminus of PKR is responsible for the activation of the NF-κB signaling pathway by interacting with the IKK complex, 10.1016/j.cellsig.2006.02.010
  177. Fontalba Ana, Gutiérrez Olga, Llorca Javier, Mateo Ignacio, Berciano José, Fernández-Luna José Luis, Combarros Onofre, Deficiency of CARD8 Is Associated with Increased Alzheimer’s Disease Risk in Women, 10.1159/000160956
  178. Paris Daniel, Patel Nikunj, Quadros Amita, Linan Monica, Bakshi Pancham, Ait-Ghezala Ghania, Mullan Michael, Inhibition of Aβ production by NF-κB inhibitors, 10.1016/j.neulet.2006.12.029
  179. Gil Jesús, Esteban Mariano, The interferon-induced protein kinase (PKR), triggers apoptosis through FADD-mediated activation of caspase 8 in a manner independent of Fas and TNF-α receptors, 10.1038/sj.onc.1203710
  180. Cantarella G, Uberti D, Carsana T, Lombardo G, Bernardini R, Memo M, Neutralization of TRAIL death pathway protects human neuronal cell line from β-amyloid toxicity, 10.1038/sj.cdd.4401143