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Inhibition of GSK-3 Ameliorates Aβ Pathology in an Adult-Onset Drosophila Model of Alzheimer's Disease

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Sofola, Oyinkan, Kerr, Fiona, Rogers, Iain, Killick, Richard, Augustin, Hrvoje, Gandy, Carina, Allen, Marcus J., Hardy, John +2 more·2010·PLoS Genetics
DOI 10.1371/journal.pgen.1001087PMC PMC2932684
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Abstract

Abeta peptide accumulation is thought to be the primary event in the pathogenesis of Alzheimer's disease (AD), with downstream neurotoxic effects including the hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3) is increasingly implicated as playing a pivotal role in this amyloid cascade. We have developed an adult-onset Drosophila model of AD, using an inducible gene expression system to express Arctic mutant Abeta42 specifically in adult neurons, to avoid developmental effects. Abeta42 accumulated with age in these flies and they displayed increased mortality together with progressive neuronal dysfunction, but in the apparent absence of neuronal loss. This fly model can thus be used to examine the role of events during adulthood and early AD aetiology. Expression of Abeta42 in adult neurons increased GSK-3 activity, and inhibition of GSK-3 (either genetically or pharmacologically by lithium treatment) rescued Abeta42 toxicity. Abeta42 pathogenesis was also reduced by removal of endogenous fly tau; but, within the limits of detection of available methods, tau phosphorylation did not appear to be altered in flies expressing Abeta42. The GSK-3-mediated effects on Abeta42 toxicity appear to be at least in part mediated by tau-independent mechanisms, because the protective effect of lithium alone was greater than that of the removal of tau alone. Finally, Abeta42 levels were reduced upon GSK-3 inhibition, pointing to a direct role of GSK-3 in the regulation of Abeta42 peptide level, in the absence of APP processing. Our study points to the need both to identify the mechanisms by which GSK-3 modulates Abeta42 levels in the fly and to determine if similar mechanisms are present in mammals, and it supports the potential therapeutic use of GSK-3 inhibitors in AD.

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  • Activities of GSK3 and PAR-1/MARKs are often associated with tau detachment from microtubules and Aβ-induced augmentation of tau toxicity.

    “the activities of two major tau kinases, GSK3 and PAR-1/microtubule affinity-regulating kinases (MARKs), are often associated with tau detachment from microtubules and Aβ-induced augmentation of tau toxicity [37, 39, 43–45].”

    From Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity (2016) · cites this paper as [44]

    The Introduction links Aβ to increased tau phosphorylation and GSK-3 activation; the Discussion identifies MARK as a kinase that phosphorylates tau. But the paper does not establish that either kinase causes tau to detach from microtubules or that PAR-1/MARK augments Aβ-induced tau toxicity. In its fly model, the Discussion reports no observable change in overall tau phosphorylation with Aβ42 expression. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Drosophila models expressing human tau recapitulate key features of human tauopathies, including progressive neurodegeneration and phosphorylation at AD-related sites via conserved kinases.

    “Drosophila models expressing human tau recapitulate key features of human tauopathies, including progressive neurodegeneration and phosphorylation at AD-related sites via conserved kinases [41, 44, 53, 59–63].”

    From Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity (2016) · cites this paper as [44]

    The Introduction describes human-tau fly models with neuronal dysfunction and reports that co-expression with Shaggy, a conserved GSK-3 homologue, worsens neurotoxic phenotypes. It does not establish progressive neurodegeneration or show that conserved kinases phosphorylate human tau at AD-related sites in those models. The Results examine phosphorylation sites on endogenous fly tau instead and find no change at the Ser262 or Ser356 homologous epitopes under the conditions tested. No page numbers are available in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • In cellular and animal models, co-expression of Aβ augments tau phosphorylation at these sites and increases the levels of active GSK3 and PAR-1/MARK.

    “In cellular and animal models, co-expression of Aβ augments tau phosphorylation at these sites and increases the levels of active GSK3 and PAR-1/MARK [2, 35–41, 43, 44].”

    From Stabilization of Microtubule-Unbound Tau via Tau Phosphorylation at Ser262/356 by Par-1/MARK Contributes to Augmentation of AD-Related Phosphorylation and Aβ42-Induced Tau Toxicity (2016) · cites this paper as [44]

    The Discussion reports that Aβ42 increased tau phosphorylation in earlier cell and mouse studies, and that Arctic Aβ42 increased GSK-3 activity in this paper's flies. But the Results found no increase in phosphorylation at the tested Ser262 and Ser356 tau sites in those flies; the paper identifies these as MARK substrates without reporting increased PAR-1/MARK activity. The citation therefore supports only part of the combined claim. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Suppression of Aβ42 toxicity supports previous reports in cell, mouse and fly models in which Aβ42 induces GSK-3β activity and inhibition or reduction of GSK-3β ameliorates Aβ42-induced degeneration.

    “Suppression of Aβ42 toxicity supports previous reports in cell, mouse and fly models in which Aβ42 induces GSK-3β activity and inhibition or reduction of GSK-3β ameliorates Aβ42-induced degeneration, either independent of or in concert with tau toxicity (99–101).”

    From Functional genomic screen and network analysis reveal novel modifiers of tauopathy dissociated from tau phosphorylation (2011) · cites this paper as [100]

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  1. [1]Spires TL Hyman BT 2005 Transgenic models of Alzheimer's disease: learning from animals. NeuroRx 2 423 437 16389306 PMC1144486
  2. [2]Selkoe DJ Schenk D 2003 Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43 545 584 12415125
  3. [4]Rizzu P Van Swieten JC Joosse M Hasegawa M Stevens M 1999 High prevalence of mutations in the microtubule-associated protein tau in a population study of frontotemporal dementia in the Netherlands. Am J Hum Genet 64 414 421 9973279 PMC1377751
  4. [5]Lewis J Dickson DW Lin WL Chisholm L Corral A 2001 Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293 1487 1491 11520987
  5. [6]Oddo S Billings L Kesslak JP Cribbs DH LaFerla FM 2004 Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome. Neuron 43 321 332 15294141
  6. [7]Oddo S Caccamo A Cheng D Jouleh B Torp R 2007 Genetically augmenting tau levels does not modulate the onset or progression of Abeta pathology in transgenic mice. J Neurochem 102 1053 1063 17472708
  7. [8]Roberson ED Scearce-Levie K Palop JJ Yan F Cheng IH 2007 Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science 316 750 754 17478722
  8. [9]Muyllaert D Kremer A Jaworski T Borghgraef P Devijver H 2008 Glycogen synthase kinase-3beta, or a link between amyloid and tau pathology? Genes Brain Behav 7 Suppl 1 57 66 18184370
  9. [10]Wang ZF Li HL Li XC Zhang Q Tian Q 2006 Effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell culture. J Neurochem 98 1167 1175 16762022
  10. [11]Forde JE Dale TC 2007 Glycogen synthase kinase 3: a key regulator of cellular fate. Cell Mol Life Sci 64 1930 1944 17530463 PMC11136264
  11. [12]Phiel CJ Wilson CA Lee VM Klein PS 2003 GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides. Nature 423 435 439 12761548
  12. [13]Lochhead PA Kinstrie R Sibbet G Rawjee T Morrice N 2006 A chaperone-dependent GSK-3beta transitional intermediate mediates activation-loop autophosphorylation. Mol Cell 24 627 633 17188038
  13. [14]Terwel D Muyllaert D Dewachter I Borghgraef P Croes S 2008 Amyloid activates GSK-3beta to aggravate neuronal tauopathy in bigenic mice. Am J Pathol 172 786 798 18258852 PMC2258274
  14. [15]Ryves WJ Harwood AJ 2001 Lithium inhibits glycogen synthase kinase-3 by competition for magnesium. Biochem Biophys Res Commun 280 720 725 11162580
  15. [16]Chalecka-Franaszek E Chuang DM 1999 Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc Natl Acad Sci U S A 96 8745 8750 10411946 PMC17587
  16. [17]Rockenstein E Torrance M Adame A Mante M Bar-on P 2007 Neuroprotective effects of regulators of the glycogen synthase kinase-3beta signaling pathway in a transgenic model of Alzheimer's disease are associated with reduced amyloid precursor protein phosphorylation. J Neurosci 27 1981 1991 17314294 PMC6673566
  17. [18]Noble W Planel E Zehr C Olm V Meyerson J 2005 Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo. Proc Natl Acad Sci U S A 102 6990 6995 15867159 PMC1088065
  18. [19]Caccamo A Oddo S Tran LX LaFerla FM 2007 Lithium reduces tau phosphorylation but not A beta or working memory deficits in a transgenic model with both plaques and tangles. Am J Pathol 170 1669 1675 17456772 PMC1854961
  19. [20]Mershin A Pavlopoulos E Fitch O Braden BC Nanopoulos DV 2004 Learning and memory deficits upon TAU accumulation in Drosophila mushroom body neurons. Learn Mem 11 277 287 15169857 PMC419730
  20. [21]Ubhi KK Shaibah H Newman TA Shepherd D Mudher A 2007 A comparison of the neuronal dysfunction caused by Drosophila tau and human tau in a Drosophila model of tauopathies. Invert Neurosci 7 165 171 17636367
  21. [22]Wittmann CW Wszolek MF Shulman JM Salvaterra PM Lewis J 2001 Tauopathy in Drosophila: neurodegeneration without neurofibrillary tangles. Science 293 711 714 11408621
  22. [23]Ruel L Bourouis M Heitzler P Pantesco V Simpson P 1993 Drosophila shaggy kinase and rat glycogen synthase kinase-3 have conserved activities and act downstream of Notch. Nature 362 557 560 8385271
  23. [24]Jackson GR Wiedau-Pazos M Sang TK Wagle N Brown CA 2002 Human wild-type tau interacts with wingless pathway components and produces neurofibrillary pathology in Drosophila. Neuron 34 509 519 12062036
  24. [26]Finelli A Kelkar A Song HJ Yang H Konsolaki M 2004 A model for studying Alzheimer's Abeta42-induced toxicity in Drosophila melanogaster. Mol Cell Neurosci 26 365 375 15234342
  25. [27]Crowther DC Page R Chandraratna D Lomas DA 2006 A Drosophila model of Alzheimer's disease. Methods Enzymol 412 234 255 17046662
  26. [28]Iijima K Liu HP Chiang AS Hearn SA Konsolaki M 2004 Dissecting the pathological effects of human Abeta40 and Abeta42 in Drosophila: a potential model for Alzheimer's disease. Proc Natl Acad Sci U S A 101 6623 6628 15069204 PMC404095
  27. [29]Rosen DR Martin-Morris L Luo LQ White K 1989 A Drosophila gene encoding a protein resembling the human beta-amyloid protein precursor. Proc Natl Acad Sci U S A 86 2478 2482 2494667 PMC286936
  28. [30]Osterwalder T Yoon KS White BH Keshishian H 2001 A conditional tissue-specific transgene expression system using inducible GAL4. Proc Natl Acad Sci U S A 98 12596 12601 11675495 PMC60099
  29. [31]McGuire SE Mao Z Davis RL 2004 Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila. Sci STKE 2004 pl6 14970377
  30. [32]Latouche M Lasbleiz C Martin E Monnier V Debeir T 2007 A conditional pan-neuronal Drosophila model of spinocerebellar ataxia 7 with a reversible adult phenotype suitable for identifying modifier genes. J Neurosci 27 2483 2492 17344386 PMC6672519
  31. [33]Crowther DC Kinghorn KJ Miranda E Page R Curry JA 2005 Intraneuronal Abeta, non-amyloid aggregates and neurodegeneration in a Drosophila model of Alzheimer's disease. Neuroscience 132 123 135 15780472
  32. [34]Bharadwaj PR Dubey AK Masters CL Martins RN Macreadie IG 2009 Abeta aggregation and possible implications in Alzheimer's disease pathogenesis. J Cell Mol Med 13 412 421 19374683 PMC3822505
  33. [35]Nilsberth C Westlind-Danielsson A Eckman CB Condron MM Axelman K 2001 The ‘Arctic’ APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nat Neurosci 4 887 893 11528419
  34. [36]Feany MB Bender WW 2000 A Drosophila model of Parkinson's disease. Nature 404 394 398 10746727
  35. [37]Papadopoulou D Bianchi MW Bourouis M 2004 Functional studies of shaggy/glycogen synthase kinase 3 phosphorylation sites in Drosophila melanogaster. Mol Cell Biol 24 4909 4919 15143183 PMC416399
  36. [38]Bourouis M 2002 Targeted increase in shaggy activity levels blocks wingless signaling. Genesis 34 99 102 12324959
  37. [39]Kinoshita E Kinoshita-Kikuta E Takiyama K Koike T 2006 Phosphate-binding tag, a new tool to visualize phosphorylated proteins. Mol Cell Proteomics 5 749 757 16340016
  38. [40]Oh H Irvine KD 2008 In vivo regulation of Yorkie phosphorylation and localization. Development 135 1081 1088 18256197 PMC2387210
  39. [41]Hanger DP Byers HL Wray S Leung KY Saxton MJ 2007 Novel phosphorylation sites in tau from Alzheimer brain support a role for casein kinase 1 in disease pathogenesis. J Biol Chem 282 23645 23654 17562708
  40. [42]Hanger DP Anderton BH Noble W 2009 Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med 15 112 119 19246243
  41. [43]Gotz J Chen F van Dorpe J Nitsch RM 2001 Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 293 1491 1495 11520988
  42. [44]Perez M Ribe E Rubio A Lim F Moran MA 2005 Characterization of a double (amyloid precursor protein-tau) transgenic: tau phosphorylation and aggregation. Neuroscience 130 339 347 15664690
  43. [45]Pennanen L Gotz J 2005 Different tau epitopes define Abeta42-mediated tau insolubility. Biochem Biophys Res Commun 337 1097 1101 16226718
  44. [46]Doerflinger H Benton R Shulman JM St Johnston D 2003 The role of PAR-1 in regulating the polarised microtubule cytoskeleton in the Drosophila follicular epithelium. Development 130 3965 3975 12874119
  45. [47]Su Y Ryder J Li B Wu X Fox N 2004 Lithium, a common drug for bipolar disorder treatment, regulates amyloid-beta precursor protein processing. Biochemistry 43 6899 6908 15170327
  46. [48]Hanger DP Hughes K Woodgett JR Brion JP Anderton BH 1992 Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase. Neurosci Lett 147 58 62 1336152
  47. [49]Mandelkow EM Drewes G Biernat J Gustke N Van Lint J 1992 Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau. FEBS Lett 314 315 321 1334849
  48. [50]Lovestone S Reynolds CH Latimer D Davis DR Anderton BH 1994 Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells. Curr Biol 4 1077 1086 7704571
  49. [51]Brownlees J Irving NG Brion JP Gibb BJ Wagner U 1997 Tau phosphorylation in transgenic mice expressing glycogen synthase kinase-3beta transgenes. Neuroreport 8 3251 3255 9351652
  50. [52]Lucas JJ Hernandez F Gomez-Ramos P Moran MA Hen R 2001 Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. Embo J 20 27 39 11226152 PMC140191
  51. [53]McGowan E Eriksen J Hutton M 2006 A decade of modeling Alzheimer's disease in transgenic mice. Trends Genet 22 281 289 16567017
  52. [54]Magrane J Rosen KM Smith RC Walsh K Gouras GK 2005 Intraneuronal beta-amyloid expression downregulates the Akt survival pathway and blunts the stress response. J Neurosci 25 10960 10969 16306409 PMC6725865
  53. [55]Folwell J Cowan CM Ubhi KK Shiabh H Newman TA Abeta exacerbates the neuronal dysfunction caused by human tau expression in a Drosophila model of Alzheimer's disease. Exp Neurol 223 401 409 19782075
  54. [56]Joutel A Tournier-Lasserve E 1998 Notch signalling pathway and human diseases. Semin Cell Dev Biol 9 619 625 10075489
  55. [57]Dierick H Bejsovec A 1999 Cellular mechanisms of wingless/Wnt signal transduction. Curr Top Dev Biol 43 153 190 9891886
  56. [58]Drewes G Ebneth A Preuss U Mandelkow EM Mandelkow E 1997 MARK, a novel family of protein kinases that phosphorylate microtubule-associated proteins and trigger microtubule disruption. Cell 89 297 308 9108484
  57. [59]Nishimura I Yang Y Lu B 2004 PAR-1 kinase plays an initiator role in a temporally ordered phosphorylation process that confers tau toxicity in Drosophila. Cell 116 671 682 15006350
  58. [60]Iijima K Gatt A Iijima-Ando K 2010 Tau Ser262 phosphorylation is critical for A{beta}42-induced tau toxicity in a transgenic Drosophila model of Alzheimer's disease. Hum Mol Genet epub ahead of print PMC2901137 20466736
  59. [61]Gomez de Barreda E Perez M Gomez Ramos P de Cristobal J Martin-Maestro P Tau-knockout mice show reduced GSK-3-induced hippocampal degeneration and learning deficits. Neurobiol Dis 37 622 629 20004245
  60. [62]Iwata N Tsubuki S Takaki Y Shirotani K Lu B 2001 Metabolic regulation of brain Abeta by neprilysin. Science 292 1550 1552 11375493
  61. [63]Farris W Mansourian S Chang Y Lindsley L Eckman EA 2003 Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A 100 4162 4167 12634421 PMC153065
  62. [64]Miller BC Eckman EA Sambamurti K Dobbs N Chow KM 2003 Amyloid-beta peptide levels in brain are inversely correlated with insulysin activity levels in vivo. Proc Natl Acad Sci U S A 100 6221 6226 12732730 PMC156353
  63. [65]Eckman EA Watson M Marlow L Sambamurti K Eckman CB 2003 Alzheimer's disease beta-amyloid peptide is increased in mice deficient in endothelin-converting enzyme. J Biol Chem 278 2081 2084 12464614
  64. [66]Melchor JP Pawlak R Strickland S 2003 The tissue plasminogen activator-plasminogen proteolytic cascade accelerates amyloid-beta (Abeta) degradation and inhibits Abeta-induced neurodegeneration. J Neurosci 23 8867 8871 14523088 PMC6740393
  65. [67]Leissring MA Farris W Chang AY Walsh DM Wu X 2003 Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40 1087 1093 14687544
  66. [68]Ho L Qin W Pompl PN Xiang Z Wang J 2004 Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease. Faseb J 18 902 904 15033922
  67. [69]Killick R Scales G Leroy K Causevic M Hooper C 2009 Deletion of Irs2 reduces amyloid deposition and rescues behavioural deficits in APP transgenic mice. Biochem Biophys Res Commun 386 257 262 19523444 PMC2726921
  68. [70]Iijima-Ando K Hearn SA Granger L Shenton C Gatt A 2008 Overexpression of neprilysin reduces alzheimer amyloid-beta42 (Abeta42)-induced neuron loss and intraneuronal Abeta42 deposits but causes a reduction in cAMP-responsive element-binding protein-mediated transcription, age-dependent axon pathology, and premature death in Drosophila. J Biol Chem 283 19066 19076 18463098 PMC2441542
  69. [71]Tsuda M Kobayashi T Matsuo T Aigaki T Insulin-degrading enzyme antagonizes insulin-dependent tissue growth and Abeta-induced neurotoxicity in Drosophila. FEBS Lett 20493190
  70. [72]He B Meng YH Mivechi NF 1998 Glycogen synthase kinase 3beta and extracellular signal-regulated kinase inactivate heat shock transcription factor 1 by facilitating the disappearance of transcriptionally active granules after heat shock. Mol Cell Biol 18 6624 6633 9774677 PMC109247
  71. [73]Cohen E Bieschke J Perciavalle RM Kelly JW Dillin A 2006 Opposing activities protect against age-onset proteotoxicity. Science 313 1604 1610 16902091
  72. [74]Allen MJ Godenschwege TA Tanouye MA Phelan P 2006 Making an escape: development and function of the Drosophila giant fibre system. Semin Cell Dev Biol 17 31 41 16378740
  73. [75]Rival T Soustelle L Strambi C Besson MT Iche M 2004 Decreasing glutamate buffering capacity triggers oxidative stress and neuropil degeneration in the Drosophila brain. Curr Biol 14 599 605 15062101
  74. [76]Ganetzky B Flanagan JR 1978 On the relationship between senescence and age-related changes in two wild-type strains of Drosophila melanogaster. Exp Gerontol 13 189 196 99324
  75. [77]Allen MJ Shan X Caruccio P Froggett SJ Moffat KG 1999 Targeted expression of truncated glued disrupts giant fiber synapse formation in Drosophila. J Neurosci 19 9374 9384 10531442 PMC6782895
  76. [78]Tanouye MA Wyman RJ 1980 Motor outputs of giant nerve fiber in Drosophila. J Neurophysiol 44 405 421 6774064
  77. [79]Gorczyca M Hall JC 1984 Identification of a cholinergic synapse in the giant fiber pathway of Drosophila using conditional mutations of acetylcholine synthesis. J Neurogenet 1 289 313 6443123
  78. [80]Burns M Gaynor K Olm V Mercken M LaFrancois J 2003 Presenilin redistribution associated with aberrant cholesterol transport enhances beta-amyloid production in vivo. J Neurosci 23 5645 5649 12843267 PMC6741250

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Authors
Sofola, O., Kerr, F., Rogers, I., Killick, R., Augustin, H., Gandy, C., Allen, M. J., Hardy, J., Lovestone, S., & Partridge, L.
Affiliations
  • Max Planck Institute for Biology of Ageing (DE)
  • University College London (GB)
  • King's College London (GB)
  • University of Kent (GB)
  • UCL Queen Square Institute of Neurology (GB)
Corresponding author
Partridge, Linda
ORCID
Venue
PLoS Genetics
Publisher
Public Library of Science (PLoS)
Published
2010-09-02
Volume
6
Issue
9
Pages
e1001087
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1001087
PMC
PMC2932684
OpenAlex
W2036225615
Cited by
174
References
2
Citations by year
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FWCI
7.58
Type
journal article
Language
en
Update notices
correction (2012-01-05)
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ResearchOnline (acceptedVersion, cc-by)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Kent Academic Repository (University of Kent) (submittedVersion)
  • Edinburgh Napier Research Repository (Edinburgh Napier University) (submittedVersion)
  • Edinburgh Napier Research Repository (Edinburgh Napier University) (submittedVersion, cc-by)
  • ResearchOnline (Glasgow Caledonian University) (submittedVersion, cc-by)
Funders
  • Wellcome Trust
  • Alzheimer's Society
  • Parkinson's UK (G-0907)
  • European Commission
  • Eisai
  • Centre National de la Recherche Scientifique
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, GSK3 inhibition, amyloid-beta 42, Drosophila model, lithium, tau protein, tau phosphorylation, amyloid hypothesis, GSK-3 inhibitors, neuronal dysfunction, mortality
MeSH terms
Aging, Alzheimer Disease, Animals, Disease Models, Animal, Drosophila melanogaster, Genes, Dominant, Humans, Lithium, Nervous System, Neurons, Peptides, Phosphorylation, Phosphoserine, Amyloid beta-Protein Precursor, tau Proteins, Drosophila Proteins, Glycogen Synthase Kinase 3, Mutant Proteins

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