mTOR: on target for novel therapeutic strategies in the nervous system

Trends in Molecular Medicine - Tập 19 - Trang 51-60 - 2013
Kenneth Maiese1,2,3, Zhao Zhong Chong1,3, Yan Chen Shang1,3, Shaohui Wang1,3
1Laboratory of Cellular and Molecular Signaling, Cancer Center, F 1220, New Jersey Health Sciences University, 205 South Orange Avenue, Newark, NJ 07101, USA
2Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
3New Jersey Health Sciences University, Newark, NJ 07101, USA

Tài liệu tham khảo

Chong, 2010, Mammalian target of rapamycin: hitting the bull's-eye for neurological disorders, Oxid. Med. Cell. Longev., 3, 374, 10.4161/oxim.3.6.14787 Brown, 1994, A mammalian protein targeted by G1-arresting rapamycin–receptor complex, Nature, 369, 756, 10.1038/369756a0 Heitman, 1991, Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast, Science, 253, 905, 10.1126/science.1715094 Chong, 2012, Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin, Prog. Neurobiol., 99, 128, 10.1016/j.pneurobio.2012.08.001 Takahashi, 2000, Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and in vitro, Genes Cells, 5, 765, 10.1046/j.1365-2443.2000.00365.x Benjamin, 2011, Rapamycin passes the torch: a new generation of mTOR inhibitors, Nat. Rev. Drug Discov., 10, 868, 10.1038/nrd3531 Acosta-Jaquez, 2009, Site-specific mTOR phosphorylation promotes mTORC1-mediated signaling and cell growth, Mol. Cell. Biol., 29, 4308, 10.1128/MCB.01665-08 Chiang, 2005, Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase, J. Biol. Chem., 280, 25485, 10.1074/jbc.M501707200 Reynolds, 2002, Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load, J. Biol. Chem., 277, 17657, 10.1074/jbc.M201142200 Soliman, 2010, mTOR Ser-2481 autophosphorylation monitors mTORC-specific catalytic activity and clarifies rapamycin mechanism of action, J. Biol. Chem., 285, 7866, 10.1074/jbc.M109.096222 Wang, 2009, Mammalian target of rapamycin complex 1 (mTORC1) activity is associated with phosphorylation of raptor by mTOR, J. Biol. Chem., 284, 14693, 10.1074/jbc.C109.002907 Wang, 2012, Proline-rich Akt substrate of 40kDa (PRAS40): a novel downstream target of PI3k/Akt signaling pathway, Cell. Signal., 24, 17, 10.1016/j.cellsig.2011.08.010 Chen, 2003, LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway, J. Cell Biol., 161, 333, 10.1083/jcb.200210141 Kim, 2003, GβL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR, Mol. Cell, 11, 895, 10.1016/S1097-2765(03)00114-X Guertin, 2006, Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCα, but not S6K1, Dev. Cell, 11, 859, 10.1016/j.devcel.2006.10.007 Peterson, 2009, DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival, Cell, 137, 873, 10.1016/j.cell.2009.03.046 Zhao, 2011, DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(βTrCP) E3 ubiquitin ligase and regulates survival and autophagy, Mol. Cell, 44, 304, 10.1016/j.molcel.2011.08.029 Sarbassov, 2005, Phosphorylation and regulation of Akt/PKB by the rictor–mTOR complex, Science, 307, 1098, 10.1126/science.1106148 Chen, 2011, The mTOR (mammalian target of rapamycin) kinase maintains integrity of mTOR complex 2, J. Biol. Chem., 286, 40386, 10.1074/jbc.M111.282590 Pearce, 2011, Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney, Biochem. J., 436, 169, 10.1042/BJ20102103 Gingras, 1998, 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway, Genes Dev., 12, 502, 10.1101/gad.12.4.502 Lenz, 2005, Glutamatergic regulation of the p70S6 kinase in primary mouse neurons, J. Biol. Chem., 280, 38121, 10.1074/jbc.C500363200 Cota, 2006, Hypothalamic mTOR signaling regulates food intake, Science, 312, 927, 10.1126/science.1124147 Sarbassov, 2004, Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton, Curr. Biol., 14, 1296, 10.1016/j.cub.2004.06.054 Gulhati, 2011, mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways, Cancer Res., 71, 3246, 10.1158/0008-5472.CAN-10-4058 Hernandez-Negrete, 2007, P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration, J. Biol. Chem., 282, 23708, 10.1074/jbc.M703771200 Cai, 2006, Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning, J. Cell Biol., 173, 279, 10.1083/jcb.200507119 Huang, 2008, The TSC1–TSC2 complex is required for proper activation of mTOR complex 2, Mol. Cell. Biol., 28, 4104, 10.1128/MCB.00289-08 Inoki, 2003, TSC2 mediates cellular energy response to control cell growth and survival, Cell, 115, 577, 10.1016/S0092-8674(03)00929-2 DeYoung, 2008, Hypoxia regulates TSC1/2–mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling, Genes Dev., 22, 239, 10.1101/gad.1617608 Murakami, 2004, mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells, Mol. Cell. Biol., 24, 6710, 10.1128/MCB.24.15.6710-6718.2004 Gangloff, 2004, Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development, Mol. Cell. Biol., 24, 9508, 10.1128/MCB.24.21.9508-9516.2004 Zhou, 2009, mTOR supports long-term self-renewal and suppresses mesoderm and endoderm activities of human embryonic stem cells, Proc. Natl. Acad. Sci. U.S.A., 106, 7840, 10.1073/pnas.0901854106 Iriuchishima, 2011, Ex vivo maintenance of hematopoietic stem cells by quiescence induction through Fbxw7α overexpression, Blood, 117, 2373, 10.1182/blood-2010-07-294801 Easley, 2010, mTOR-mediated activation of p70 S6K induces differentiation of pluripotent human embryonic stem cells, Cell. Reprogramm., 12, 263, 10.1089/cell.2010.0011 Han, 2008, Mammalian target of rapamycin (mTOR) is involved in the neuronal differentiation of neural progenitors induced by insulin, Mol. Cell. Neurosci., 39, 118, 10.1016/j.mcn.2008.06.003 Malagelada, 2011, RTP801/REDD1 regulates the timing of cortical neurogenesis and neuron migration, J. Neurosci., 31, 3186, 10.1523/JNEUROSCI.4011-10.2011 Magri, 2011, Sustained activation of mTOR pathway in embryonic neural stem cells leads to development of tuberous sclerosis complex-associated lesions, Cell Stem Cell, 9, 447, 10.1016/j.stem.2011.09.008 Maiese, 2005, New avenues of exploration for erythropoietin, JAMA, 293, 90, 10.1001/jama.293.1.90 Shang, 2011, Erythropoietin and Wnt1 govern pathways of mTOR, Apaf-1, and XIAP in inflammatory microglia, Curr. Neurovasc. Res., 8, 270, 10.2174/156720211798120990 Kim, 2012, Erythropoietin mediated bone formation is regulated by mTOR signaling, J. Cell. Biochem., 113, 220, 10.1002/jcb.23347 Miriuka, 2006, mTOR inhibition induces endothelial progenitor cell death, Am. J. Transplant., 6, 2069, 10.1111/j.1600-6143.2006.01433.x Sato, 2010, Regulation of neural stem/progenitor cell maintenance by PI3K and mTOR, Neurosci. Lett., 470, 115, 10.1016/j.neulet.2009.12.067 Maiese, 2008, The Wnt signaling pathway: aging gracefully as a protectionist?, Pharmacol. Ther., 118, 58, 10.1016/j.pharmthera.2008.01.004 Inoki, 2006, TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth, Cell, 126, 955, 10.1016/j.cell.2006.06.055 Huang, 2009, Pivotal role for glycogen synthase kinase-3 in hematopoietic stem cell homeostasis in mice, J. Clin. Invest., 119, 3519 Chong, 2005, Oxidative stress in the brain: novel cellular targets that govern survival during neurodegenerative disease, Prog. Neurobiol., 75, 207, 10.1016/j.pneurobio.2005.02.004 Zengi, 2011, Increased oxidative DNA damage in lean normoglycemic offspring of type 2 diabetic patients, Exp. Clin. Endocrinol. Diabetes, 119, 467, 10.1055/s-0031-1275289 Vendelbo, 2011, Mitochondrial longevity pathways, Biochim. Biophys. Acta, 1813, 634, 10.1016/j.bbamcr.2011.01.029 Tupe, 2011, Dietary nicotinic acid supplementation improves hepatic zinc uptake and offers hepatoprotection against oxidative damage, Br. J. Nutr., 25, 1 Maiese, 2010, Oxidative stress: biomarkers and novel therapeutic pathways, Exp. Gerontol., 45, 217, 10.1016/j.exger.2010.01.004 Maiese, 2012, Targeting disease through novel pathways of apoptosis and autophagy, Expert Opin. Ther. Targets, 16, 1203, 10.1517/14728222.2012.719499 Louneva, 2008, Caspase-3 is enriched in postsynaptic densities and increased in Alzheimer's disease, Am. J. Pathol., 173, 1488, 10.2353/ajpath.2008.080434 Tatton, 2000, Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson's disease, Exp. Neurol., 166, 29, 10.1006/exnr.2000.7489 Canu, 2005, Role of the autophagic-lysosomal system on low potassium-induced apoptosis in cultured cerebellar granule cells, J. Neurochem., 92, 1228, 10.1111/j.1471-4159.2004.02956.x Qin, 2010, Autophagy was activated in injured astrocytes and mildly decreased cell survival following glucose and oxygen deprivation and focal cerebral ischemia, Autophagy, 6, 738, 10.4161/auto.6.6.12573 Wang, 2011, Severe global cerebral ischemia-induced programmed necrosis of hippocampal CA1 neurons in rat is prevented by 3-methyladenine: a widely used inhibitor of autophagy, J. Neuropathol. Exp. Neurol., 70, 314, 10.1097/NEN.0b013e31821352bd Baba, 2009, Autophagy-mediated stress response in motor neuron after transient ischemia in rabbits, J. Vasc. Surg., 50, 381, 10.1016/j.jvs.2009.03.042 Spencer, 2009, Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson's and Lewy body diseases, J. Neurosci., 29, 13578, 10.1523/JNEUROSCI.4390-09.2009 Spilman, 2010, Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease, PLoS ONE, 5, e9979, 10.1371/journal.pone.0009979 Jeong, 2012, Autophagy induced by resveratrol prevents human prion protein-mediated neurotoxicity, Neurosci. Res., 73, 99, 10.1016/j.neures.2012.03.005 Chen, 2010, Hydrogen peroxide inhibits mTOR signaling by activation of AMPKα leading to apoptosis of neuronal cells, Lab. Invest., 90, 762, 10.1038/labinvest.2010.36 Wu, 2004, Insulin promotes rat retinal neuronal cell survival in a p70S6K-dependent manner, J. Biol. Chem., 279, 9167, 10.1074/jbc.M312397200 Shang, 2012, Prevention of beta-amyloid degeneration of microglia by erythropoietin depends on Wnt1, the PI 3-K/mTOR pathway, Bad, and Bcl-xL, Aging (Albany NY), 4, 187, 10.18632/aging.100440 Chong, 2007, The pro-survival pathways of mTOR and protein kinase B target glycogen synthase kinase-3β and nuclear factor-κB to foster endogenous microglial cell protection, Int. J. Mol. Med., 19, 263 Pastor, 2009, mTOR/S6 kinase pathway contributes to astrocyte survival during ischemia, J. Biol. Chem., 284, 22067, 10.1074/jbc.M109.033100 Choi, 2010, A novel mTOR activating protein protects dopamine neurons against oxidative stress by repressing autophagy related cell death, J. Neurochem., 112, 366, 10.1111/j.1471-4159.2009.06463.x Chong, 2012, PRAS40 is an integral regulatory component of erythropoietin mTOR signaling and cytoprotection, PLoS ONE, 7, e45456, 10.1371/journal.pone.0045456 Nascimento, 2010, Phosphorylation of PRAS40 on Thr246 by PKB/AKT facilitates efficient phosphorylation of Ser183 by mTORC1, Cell. Signal., 22, 961, 10.1016/j.cellsig.2010.02.002 Carayol, 2010, Critical roles for mTORC2- and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells, Proc. Natl. Acad. Sci. U.S.A., 107, 12469, 10.1073/pnas.1005114107 Luo, 2010, Apoptosis blocks Beclin 1-dependent autophagosome synthesis: an effect rescued by Bcl-xL, Cell Death Differ., 17, 268, 10.1038/cdd.2009.121 Wang, 2012, WISP1 (CCN4) autoregulates its expression and nuclear trafficking of beta-catenin during oxidant stress with limited effects upon neuronal autophagy, Curr. Neurovasc. Res., 9, 89, 10.2174/156720212800410858 Le, 2010, Dasatinib induces autophagic cell death in human ovarian cancer, Cancer, 116, 4980, 10.1002/cncr.25426 Salminen, 2011, AMP-activated protein kinase: a potential player in Alzheimer's disease, J. Neurochem., 118, 460, 10.1111/j.1471-4159.2011.07331.x Yu, 2010, Termination of autophagy and reformation of lysosomes regulated by mTOR, Nature, 465, 942, 10.1038/nature09076 Rong, 2011, Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation, Proc. Natl. Acad. Sci. U.S.A., 108, 7826, 10.1073/pnas.1013800108 Jung, 2009, ULK–Atg13–FIP200 complexes mediate mTOR signaling to the autophagy machinery, Mol. Biol. Cell, 20, 1992, 10.1091/mbc.E08-12-1249 Hosokawa, 2009, Atg101, a novel mammalian autophagy protein interacting with Atg13, Autophagy, 5, 973, 10.4161/auto.5.7.9296 Slipczuk, 2009, BDNF activates mTOR to regulate GluR1 expression required for memory formation, PLoS ONE, 4, e6007, 10.1371/journal.pone.0006007 Griffin, 2005, Activation of Akt/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer's disease pathology, J. Neurochem., 93, 105, 10.1111/j.1471-4159.2004.02949.x An, 2003, Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease, Am. J. Pathol., 163, 591, 10.1016/S0002-9440(10)63687-5 Paccalin, 2006, Activated mTOR and PKR kinases in lymphocytes correlate with memory and cognitive decline in Alzheimer's disease, Dement. Geriatr. Cogn. Disord., 22, 320, 10.1159/000095562 Ma, 2010, Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease, PLoS ONE, 5, e12845, 10.1371/journal.pone.0012845 Lafay-Chebassier, 2005, mTOR/p70S6k signalling alteration by Aβ exposure as well as in APP-PS1 transgenic models and in patients with Alzheimer's disease, J. Neurochem., 94, 215, 10.1111/j.1471-4159.2005.03187.x Chano, 2007, RB1CC1 insufficiency causes neuronal atrophy through mTOR signaling alteration and involved in the pathology of Alzheimer's diseases, Brain Res., 1168, 97, 10.1016/j.brainres.2007.06.075 Imai, 2008, Phosphorylation of 4E-BP by LRRK2 affects the maintenance of dopaminergic neurons in Drosophila, EMBO J., 27, 2432, 10.1038/emboj.2008.163 Tain, 2009, Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss, Nat. Neurosci., 12, 1129, 10.1038/nn.2372 Malagelada, 2006, RTP801 is elevated in Parkinson brain substantia nigral neurons and mediates death in cellular models of Parkinson's disease by a mechanism involving mammalian target of rapamycin inactivation, J. Neurosci., 26, 9996, 10.1523/JNEUROSCI.3292-06.2006 Crews, 2010, Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of alpha-synucleinopathy, PLoS ONE, 5, e9313, 10.1371/journal.pone.0009313 Santini, 2009, Inhibition of mTOR signaling in Parkinson's disease prevents l-DOPA-induced dyskinesia, Sci. Signal., 2, ra36, 10.1126/scisignal.2000308 Berger, 2006, Rapamycin alleviates toxicity of different aggregate-prone proteins, Hum. Mol. Genet., 15, 433, 10.1093/hmg/ddi458 Ravikumar, 2004, Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease, Nat. Genet., 36, 585, 10.1038/ng1362 Floto, 2007, Small molecule enhancers of rapamycin-induced TOR inhibition promote autophagy, reduce toxicity in Huntington's disease models and enhance killing of mycobacteria by macrophages, Autophagy, 3, 620, 10.4161/auto.4898 Roscic, 2011, Induction of autophagy with catalytic mTOR inhibitors reduces huntingtin aggregates in a neuronal cell model, J. Neurochem., 119, 398, 10.1111/j.1471-4159.2011.07435.x Fox, 2010, The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease, Mol. Neurodegener., 5, 26, 10.1186/1750-1326-5-26 Hyrskyluoto, 2012, GADD34 mediates cytoprotective autophagy in mutant huntingtin expressing cells via the mTOR pathway, Exp. Cell Res., 318, 33, 10.1016/j.yexcr.2011.08.020 Holmes, 2007, Tuberous sclerosis complex and epilepsy: recent developments and future challenges, Epilepsia, 48, 617, 10.1111/j.1528-1167.2007.01035.x Jozwiak, 2009, Fibroblasts from normal skin of a tuberous sclerosis patient show upregulation of mTOR pathway, Am. J. Dermatopathol., 31, 68, 10.1097/DAD.0b013e3181882c09 Waltereit, 2006, Enhanced episodic-like memory and kindling epilepsy in a rat model of tuberous sclerosis, J. Neurochem., 96, 407, 10.1111/j.1471-4159.2005.03538.x Zeng, 2008, Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex, Ann. Neurol., 63, 444, 10.1002/ana.21331 Buckmaster, 2009, Inhibition of the mammalian target of rapamycin signaling pathway suppresses dentate granule cell axon sprouting in a rodent model of temporal lobe epilepsy, J. Neurosci., 29, 8259, 10.1523/JNEUROSCI.4179-08.2009 Zeng, 2009, The mammalian target of rapamycin signaling pathway mediates epileptogenesis in a model of temporal lobe epilepsy, J. Neurosci., 29, 6964, 10.1523/JNEUROSCI.0066-09.2009 Curran, 2012, Everolimus: in patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex, Paediatr. Drugs, 14, 51, 10.2165/11207730-000000000-00000 Krueger, 2010, Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis, N. Engl. J. Med., 363, 1801, 10.1056/NEJMoa1001671 Pavel, 2011, Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study, Lancet, 378, 2005, 10.1016/S0140-6736(11)61742-X Jin, 2009, Dual inhibition of mitogen-activated protein kinase kinase and mammalian target of rapamycin in differentiated and anaplastic thyroid cancer, J. Clin. Endocrinol. Metab., 94, 4107, 10.1210/jc.2009-0662 Gulhati, 2012, Sorafenib enhances the therapeutic efficacy of rapamycin in colorectal cancers harboring oncogenic KRAS and PIK3CA, Carcinogenesis, 33, 1782, 10.1093/carcin/bgs203 Mi, 2009, Efficacy of combined inhibition of mTOR and ERK/MAPK pathways in treating a tuberous sclerosis complex cell model, J. Genet. Genomics, 36, 355, 10.1016/S1673-8527(08)60124-1 Fokas, 2012, NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity, Radiat. Oncol., 7, 48, 10.1186/1748-717X-7-48 Barrett, 2012, Targeting the PI3K/AKT/mTOR signaling axis in children with hematologic malignancies, Paediatr. Drugs, 14, 299 Grzybowska-Izydorczyk, 2012, mTOR kinase inhibitors as a treatment strategy in hematological malignancies, Future Med. Chem., 4, 487, 10.4155/fmc.12.14 Majumder, 2011, Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits, PLoS ONE, 6, e25416, 10.1371/journal.pone.0025416