PI3-kinase/Akt/mTOR signaling: Impaired on/off switches in aging, cognitive decline and Alzheimer's disease

Arendt, 2003, Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways: the ‘Dr. Jekyll and Mr. Hyde concept’ of Alzheimer's disease or the yin and yang of neuroplasticity, Prog. Neurobiol., 71, 83, 10.1016/j.pneurobio.2003.09.007 Bhaskar, 2009, The PI3K–Akt–mTOR pathway regulates Abeta oligomer induced neuronal cell cycle events, Mol. Neurodegener., 4, 14, 10.1186/1750-1326-4-14 Bomfim, 2012, An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease-associated Abeta oligomers, J. Clin. Invest., 122, 1339, 10.1172/JCI57256 Bonafe, 2003, Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control, J. Clin. Endocrinol. Metab., 88, 3299, 10.1210/jc.2002-021810 Bradley, 2012, A pivotal role of GSK-3 in synaptic plasticity, Front. Mol. Neurosci., 5, 13, 10.3389/fnmol.2012.00013 Caccamo, 2010, Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments, J. Biol. Chem., 285, 13107, 10.1074/jbc.M110.100420 Caccamo, 2011, Naturally secreted amyloid-beta increases mammalian target of rapamycin (mTOR) activity via a PRAS40-mediated mechanism, J. Biol. Chem., 286, 8924, 10.1074/jbc.M110.180638 Chiang, 2010, PI3 kinase signaling is involved in Abeta-induced memory loss in Drosophila, Proc. Natl. Acad. Sci. U. S. A., 107, 7060, 10.1073/pnas.0909314107 Cohen, 2009, Reduced IGF-1 signaling delays age-associated proteotoxicity in mice, Cell, 139, 1157, 10.1016/j.cell.2009.11.014 Craft, 2005, Insulin resistance syndrome and Alzheimer's disease: age- and obesity-related effects on memory, amyloid, and inflammation, Neurobiol. Aging, 26, 65, 10.1016/j.neurobiolaging.2005.08.021 Craft, 2012, Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial, Arch. Neurol., 69, 29, 10.1001/archneurol.2011.233 De Felice, 2009, Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers, Proc. Natl. Acad. Sci. U. S. A., 106, 1971, 10.1073/pnas.0809158106 de la Monte, 2012, Brain insulin resistance and deficiency as therapeutic targets in Alzheimer's disease, Curr. Alzheimer Res., 9, 35, 10.2174/156720512799015037 Douglas, 2010, Protein homeostasis and aging in neurodegeneration, J. Cell Biol., 190, 719, 10.1083/jcb.201005144 Ehninger, 2009, From mTOR to cognition: molecular and cellular mechanisms of cognitive impairments in tuberous sclerosis, J. Intellect. Disabil. Res., 53, 838, 10.1111/j.1365-2788.2009.01208.x Flachsbart, 2009, Association of FOXO3A variation with human longevity confirmed in German centenarians, Proc. Natl. Acad. Sci. U. S. A., 106, 2700, 10.1073/pnas.0809594106 Franke, 2008, PI3K/Akt: getting it right matters, Oncogene, 27, 6473, 10.1038/onc.2008.313 Garelick, 2011, TOR on the brain, Exp. Gerontol., 46, 155, 10.1016/j.exger.2010.08.030 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 Harrison, 2009, Rapamycin fed late in life extends lifespan in genetically heterogeneous mice, Nature, 460, 392, 10.1038/nature08221 Hers, 2011, Akt signalling in health and disease, Cell. Signal., 23, 1515, 10.1016/j.cellsig.2011.05.004 Holtzman, 2011, Alzheimer's disease: the challenge of the second century, Sci. Transl. Med., 3, 77sr71, 10.1126/scitranslmed.3002369 Holzenberger, 2003, IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice, Nature, 421, 182, 10.1038/nature01298 Hoyer, 1998, Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis, J. Neural Transm., 105, 415, 10.1007/s007020050067 Huang, 2012, Alzheimer mechanisms and therapeutic strategies, Cell, 148, 1204, 10.1016/j.cell.2012.02.040 Ittner, 2011, Amyloid-beta and tau—a toxic pas de deux in Alzheimer's disease, Nat. Rev. Neurosci., 12, 65, 10.1038/nrn2967 Ittner, 2010, Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models, Cell, 142, 387, 10.1016/j.cell.2010.06.036 Jiang, 2005, Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3beta and its upstream regulators, Cell, 120, 123 Johnson, 2008, Caenorhabditis elegans 2007: the premier model for the study of aging, Exp. Gerontol., 43, 1 Kenyon, 2010, The genetics of ageing, Nature, 464, 504, 10.1038/nature08980 Kenyon, 2012, The first long-lived mutants: discovery of the insulin/IGF-1 pathway for ageing, Philos. Trans. R. Soc. Lond. B Biol. Sci., 366, 9, 10.1098/rstb.2010.0276 Kloet, 2011, The PKB/FOXO switch in aging and cancer, Biochim. Biophys. Acta, 1813, 1926, 10.1016/j.bbamcr.2011.04.003 Kwak, 2010, NO signaling and S-nitrosylation regulate PTEN inhibition in neurodegeneration, Mol. Neurodegener., 5, 49, 10.1186/1750-1326-5-49 Li, 2005, Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain, FEBS J., 272, 4211, 10.1111/j.1742-4658.2005.04833.x Long-Smith, 2013, The diabetes drug liraglutide ameliorates aberrant insulin receptor localisation and signalling in parallel with decreasing both amyloid-beta plaque and glial pathology in a mouse model of Alzheimer's disease, Neuromolecular Med., 15, 102, 10.1007/s12017-012-8199-5 Ma, 2009, Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin, J. Neurosci., 29, 9078, 10.1523/JNEUROSCI.1071-09.2009 Majumder, 2012, Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1beta and enhancing NMDA signaling, Aging Cell, 11, 326, 10.1111/j.1474-9726.2011.00791.x Martin, 2012, IRS-2 deficiency impairs NMDA receptor-dependent long-term potentiation, Cereb. Cortex, 22, 1717, 10.1093/cercor/bhr216 McClean, 2011, The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease, J. Neurosci., 31, 6587, 10.1523/JNEUROSCI.0529-11.2011 Moloney, 2010, Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer's disease indicate possible resistance to IGF-1 and insulin signalling, Neurobiol. Aging, 31, 224, 10.1016/j.neurobiolaging.2008.04.002 Morita, 2009, Specification of neuronal polarity regulated by local translation of CRMP2 and Tau via the mTOR–p70S6K pathway, J. Biol. Chem., 284, 27734, 10.1074/jbc.M109.008177 Morris, 2011, The many faces of tau, Neuron, 70, 410, 10.1016/j.neuron.2011.04.009 O'Neill, 2012, Insulin and IGF-1 signalling: longevity, protein homoeostasis and Alzheimer's disease, Biochem. Soc. Trans., 40, 721, 10.1042/BST20120080 Pei, 2008, mTOR-dependent signalling in Alzheimer's disease, J. Cell. Mol. Med., 12, 2525, 10.1111/j.1582-4934.2008.00509.x Pei, 2003, Role of protein kinase B in Alzheimer's neurofibrillary pathology, Acta Neuropathol. (Berl.), 105, 381, 10.1007/s00401-002-0657-y Peineau, 2007, LTP inhibits LTD in the hippocampus via regulation of GSK3beta, Neuron, 53, 703, 10.1016/j.neuron.2007.01.029 Perry, 2003, Glucagon-like peptide-1 decreases endogenous amyloid-beta peptide (Abeta) levels and protects hippocampal neurons from death induced by Abeta and iron, J. Neurosci. Res., 72, 603, 10.1002/jnr.10611 Roberson, 2011, Amyloid-beta/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer's disease, J. Neurosci., 31, 700, 10.1523/JNEUROSCI.4152-10.2011 Selkoe, 2012, Deciphering Alzheimer disease, Cold Spring Harb. Perspect. Med., 2, a011460, 10.1101/cshperspect.a011460 Selman, 2009, Ribosomal protein S6 kinase 1 signaling regulates mammalian life span, Science, 326, 140, 10.1126/science.1177221 Shah, 2004, Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies, Curr. Biol., 14, 1650, 10.1016/j.cub.2004.08.026 Sonoda, 2010, Accumulation of tumor-suppressor PTEN in Alzheimer neurofibrillary tangles, Neurosci. Lett., 471, 20, 10.1016/j.neulet.2009.12.078 Suh, 2008, Functionally significant insulin-like growth factor I receptor mutations in centenarians, Proc. Natl. Acad. Sci. U. S. A., 105, 3438, 10.1073/pnas.0705467105 Talbot, 2012, Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline, J. Clin. Invest., 122, 1316, 10.1172/JCI59903 Tanti, 2009, Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation, Curr. Opin. Pharmacol., 9, 753, 10.1016/j.coph.2009.07.004 Townsend, 2007, Soluble abeta inhibits specific signal transduction cascades common to the insulin receptor pathway, J. Biol. Chem., 282, 33305, 10.1074/jbc.M610390200 van Heemst, 2005, Reduced insulin/IGF-1 signalling and human longevity, Aging Cell, 4, 79, 10.1111/j.1474-9728.2005.00148.x Westmark, 2007, FMRP mediates mGluR5-dependent translation of amyloid precursor protein, PLoS Biol., 5, e52, 10.1371/journal.pbio.0050052 Wu, 2011, mTOR complex 2 targets Akt for proteasomal degradation via phosphorylation at the hydrophobic motif, J. Biol. Chem., 286, 14190, 10.1074/jbc.M111.219923 Yoshimura, 2006, Signaling networks in neuronal polarization, J. Neurosci., 26, 10626, 10.1523/JNEUROSCI.3824-06.2006 Zhang, 2006, Tumor-suppressor PTEN affects tau phosphorylation, aggregation, and binding to microtubules, FASEB J., 20, 1272, 10.1096/fj.06-5721fje Zhao, 2008, Amyloid beta oligomers induce impairment of neuronal insulin receptors, FASEB J., 22, 246, 10.1096/fj.06-7703com Zhao, 2009, Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric a{beta}, J. Biol. Chem., 284, 18742, 10.1074/jbc.M109.011015