Clusterin regulates β-amyloid toxicity via Dickkopf-1-driven induction of the wnt–PCP–JNK pathway
Open accessAbstract
Although the mechanism of Aβ action in the pathogenesis of Alzheimer's disease (AD) has remained elusive, it is known to increase the expression of the antagonist of canonical wnt signalling, Dickkopf-1 (Dkk1), whereas the silencing of Dkk1 blocks Aβ neurotoxicity. We asked if clusterin, known to be regulated by wnt, is part of an Aβ/Dkk1 neurotoxic pathway. Knockdown of clusterin in primary neurons reduced Aβ toxicity and DKK1 upregulation and, conversely, Aβ increased intracellular clusterin and decreased clusterin protein secretion, resulting in the p53-dependent induction of DKK1. To further elucidate how the clusterin-dependent induction of Dkk1 by Aβ mediates neurotoxicity, we measured the effects of Aβ and Dkk1 protein on whole-genome expression in primary neurons, finding a common pathway suggestive of activation of wnt-planar cell polarity (PCP)-c-Jun N-terminal kinase (JNK) signalling leading to the induction of genes including EGR1 (early growth response-1), NAB2 (Ngfi-A-binding protein-2) and KLF10 (Krüppel-like factor-10) that, when individually silenced, protected against Aβ neurotoxicity and/or tau phosphorylation. Neuronal overexpression of Dkk1 in transgenic mice mimicked this Aβ-induced pathway and resulted in age-dependent increases in tau phosphorylation in hippocampus and cognitive impairment. Furthermore, we show that this Dkk1/wnt-PCP-JNK pathway is active in an Aβ-based mouse model of AD and in AD brain, but not in a tau-based mouse model or in frontotemporal dementia brain. Thus, we have identified a pathway whereby Aβ induces a clusterin/p53/Dkk1/wnt-PCP-JNK pathway, which drives the upregulation of several genes that mediate the development of AD-like neuropathologies, thereby providing new mechanistic insights into the action of Aβ in neurodegenerative diseases.
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CLU knockdown leads to reduced Aβ toxicity through involvement of the Wnt-PCP-JNK pathway.
“CLU has also been associated with the regulation of Aβ toxicity, where its knockdown leads to reduced toxicity through the involvement of Wnt-PCP-JNK pathway [70].”
From The new genetic landscape of Alzheimer’s disease: from amyloid cascade to genetically driven synaptic failure hypothesis? (2019) · cites this paper as [70]
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Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326 · see citing works
Self-citationAmyloid deposition as the central event in the aetiology of Alzheimer’s disease
Hardy, J., & Allsop, D. (1991) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(91)90609-v · Cited by 2,538 · see citing works
Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow
Bafico, A., Liu, G., Yaniv, A., Gazit, A., & Aaronson, S. A. (2001) · Nature Cell Biology · doi:10.1038/35083081 · Cited by 772 · see citing works
Genetic Control of Human Brain Transcript Expression in Alzheimer Disease
Webster, J. A., Gibbs, J. R., Clarke, J., Ray, M., Zhang, W., Holmans, P., Rohrer, K., Zhao, A., Marlowe, L., Kaleem, M., et al. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.03.011 · Cited by 304 · see citing works
Gene expression profiling in the adult Down syndrome brain
Lockstone, H. E., Harris, L. W., Swatton, J. E., Wayland, M. T., Holland, A. J., & Bahn, S. (2007) · Genomics · doi:10.1016/j.ygeno.2007.08.005 · Cited by 240 · see citing works
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Research works printed but not linked: 55
- Glenner GG Wong CW Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein Biochem Biophys Res Commun 1984 122 1131 1135 6236805
- Brion JP Flament-Durand J Dustin P Alzheimer's disease and tau proteins Lancet 1986 2 1098 2877247
- Hardy J The amyloid hypothesis for Alzheimer's disease: a critical reappraisal J Neurochem 2009 110 1129 1134 19457065
- Kremer A Louis JV Jaworski T F VanLeuven GSK3 and Alzheimer's disease: facts and fiction Front Mol Neurosci 2011 4 17 21904524 PMC3162188
- Kang DE Soriano S Xia X Eberhart CG De Strooper B Zheng H Presenilin couples the paired phosphorylation of beta-catenin independent of axin: implications for beta-catenin activation in tumorigenesis Cell 2002 110 751 762 12297048
- Alvarez AR Godoy JA Mullendorff K Olivares GH Bronfman M Inestrosa NC Wnt-3a overcomes beta-amyloid toxicity in rat hippocampal neurons Exp Cell Res 2004 297 186 196 15194435
- Caricasole A Copani A Caraci F Aronica E Rozemuller AJ Caruso A Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer's brain J Neurosci 2004 24 6021 6027 15229249 PMC6729239
- Toledo EM Inestrosa NC Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1DeltaE9 mouse model of Alzheimer's disease Mol Psychiatry 2010 15 272 285,228. 19621015
- De Ferrari GV Papassotiropoulos A Biechele T Wavrant De-Vrieze F Avila ME Major MB Common genetic variation within the low-density lipoprotein receptor-related protein 6 and late-onset Alzheimer's disease Proc Natl Acad Sci USA 2007 104 9434 9439 17517621 PMC1890512
- Mudher A Chapman S Richardson J Asuni A Gibb G Pollard C Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogen-activated protein kinase and c-Jun terminal kinase J Neurosci 2001 21 4987 4995 11438574 PMC6762860
- Killick R Pollard CC Asuni AA Mudher AK Richardson JC Rupniak HT Presenilin 1 independently regulates beta-catenin stability and transcriptional activity J Biol Chem 2001 276 48554 48561 11606587
- Rosen EY Wexler EM Versano R Coppola G Gao F Winden KD Functional genomic analyses identify pathways dysregulated by progranulin deficiency, implicating Wnt signaling Neuron 2011 71 1030 1042 21943601 PMC3633414
- Chen S Guttridge DC You Z Zhang Z Fribley A Mayo MW Wnt-1 signaling inhibits apoptosis by activating beta-catenin/T cell factor-mediated transcription J Cell Biol 2001 152 87 96 11149923 PMC2193656
- Purro SA Dickins EM Salinas PC The Secreted Wnt antagonist Dickkopf-1 is required for amyloid beta-mediated synaptic loss J Neurosci 2012 32 3492 3498 22399772 PMC6621056
- Lambert JC Heath S Even G Campion D Sleegers K Hiltunen M Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease Nat Genet 2009 41 1094 1099 19734903
- Koch-Brandt C Morgans C Clusterin: a role in cell survival in the face of apoptosis Prog Mol Subcell Biol 1996 16 130 149 8822796
- Rosi MC Luccarini I Grossi C Fiorentini A Spillantini MG Prisco A Increased Dickkopf-1 expression in transgenic mouse models of neurodegenerative disease J Neurochem 2010 112 1539 1551 20050968
- Thambisetty M Simmons A Velayudhan L Hye A Campbell J Zhang Y Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease Arch Gen Psychiatry 2010 67 739 748 20603455 PMC3111021
- Schrijvers EM Koudstaal PJ Hofman A Breteler MM Plasma clusterin and the risk of Alzheimer disease JAMA 2011 305 1322 1326 21467285
- Schepeler T Mansilla F Christensen LL Orntoft TF Andersen CL Clusterin expression can be modulated by changes in TCF1-mediated Wnt signaling J Mol Signal 2007 2 6 17634137 PMC1976611
- Gonzalez-Sancho JM Aguilera O Garcia JM Pendas-Franco N Pena C Cal S The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin/TCF and is downregulated in human colon cancer Oncogene 2005 24 1098 1103 15592505
- Theuns J Remacle J Killick R Corsmit E Vennekens K Huylebroeck D Alzheimer-associated C allele of the promoter polymorphism -22C>T causes a critical neuron-specific decrease of presenilin 1 expression Hum Mol Genet 2003 12 869 877 12668610
- Tizon B Ribe EM Mi W Troy CM Levy E Cystatin C protects neuronal cells from amyloid-beta-induced toxicity J Alzheimers Dis 2010 19 885 894 20157244 PMC2889175
- Reynolds A Leake D Boese Q Scaringe S Marshall WS Khvorova A Rational siRNA design for RNA interference Nat Biotechnol 2004 22 326 330 14758366
- Davidson TJ Harel S Arboleda VA Prunell GF Shelanski ML Greene LA Highly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation J Neurosci 2004 24 10040 10046 15537872 PMC6730191
- Killick R Scales G Leroy K Causevic M Hooper C Irvine EE Deletion of Irs2 reduces amyloid deposition and rescues behavioural deficits in APP transgenic mice Biochem Biophys Res Commun 2009 386 257 262 19523444 PMC2726921
- Livak KJ Schmittgen TD Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method Methods 2001 25 402 408 11846609
- Trougakos IP So A Jansen B Gleave ME Gonos ES Silencing expression of the clusterin/apolipoprotein j gene in human cancer cells using small interfering RNA induces spontaneous apoptosis, reduced growth ability, and cell sensitization to genotoxic and oxidative stress Cancer Res 2004 64 1834 1842 14996747
- Bertram L Tanzi RE Alzheimer disease: new light on an old CLU Nat Rev Neurol 2010 6 11 13 20057494 PMC2860389
- Hooper C Killick R Fernandes C Sugden D Lovestone S Transcriptomic profiles of Wnt3a and insulin in primary cultured rat cortical neurones J Neurochem 2011 118 512 520 21668888
- Millucci L Ghezzi L Bernardini G Santucci A Conformations and biological activities of amyloid beta peptide 25-35 Curr Protein Pept Sci 2009 11 54 67 20201807
- Abeti R Abramov AY Duchen MR Beta-amyloid activates PARP causing astrocytic metabolic failure and neuronal death Brain 2011 134 (Pt 6 1658 1672 21616968
- Lu Y Li T Qureshi HY Han D Paudel HK Early growth response 1 (Egr-1) regulates phosphorylation of microtubule-associated protein tau in mammalian brain J Biol Chem 2011 286 20569 20581 21489990 PMC3121503
- Kumbrink J Kirsch KH JP Johnson EGR1, EGR2, and EGR3 activate the expression of their coregulator NAB2 establishing a negative feedback loop in cells of neuroectodermal and epithelial origin J Cell Biochem 2010 111 207 217 20506119 PMC2930072
- Svaren J Sevetson BR Golda T Stanton JJ Swirnoff AH Milbrandt J Novel mutants of NAB corepressors enhance activation by Egr transactivators EMBO J 1998 17 6010 6019 9774344 PMC1170927
- Hsiao K Chapman P Nilsen S Eckman C Harigaya Y Younkin S Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice Science 1996 274 99 102 8810256
- Andorfer C Kress Y Espinoza M de Silva R Tucker KL Barde YA Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms J Neurochem 2003 86 582 590 12859672
- Liang WS Dunckley T Beach TG Grover A Mastroeni D Ramsey K Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: a reference data set Physiol Genomics 2008 33 240 256 18270320 PMC2826117
- Huang Y Sun X Hu G An integrated genetics approach for identifying protein signal pathways of Alzheimer's disease Comput Methods Biomech Biomed Engin 2011 14 371 378 21442495
- Ideker T Ozier O Schwikowski B Siegel AF Discovering regulatory and signalling circuits in molecular interaction networks Bioinformatics 2002 18 (Suppl 1 S233 S240 12169552
- Bertrand J Plouffe V Senechal P Leclerc N The pattern of human tau phosphorylation is the result of priming and feedback events in primary hippocampal neurons Neuroscience 2010 168 323 334 20394726
- Korol O Gupta RW Mercola M A novel activity of the Dickkopf-1 amino terminal domain promotes axial and heart development independently of canonical Wnt inhibition Dev Biol 2008 324 131 138 18840423 PMC3038239
- Krupnik VE Sharp JD Jiang C Robison K Chickering TW Amaravadi L Functional and structural diversity of the human Dickkopf gene family Gene 1999 238 301 313 10570958
- Mao B Wu W Li Y Hoppe D Stannek P Glinka A LDL-receptor-related protein 6 is a receptor for Dickkopf proteins Nature 2001 411 321 325 11357136
- Semenov MV Tamai K Brott BK Kuhl M Sokol S He X Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6 Curr Biol 2001 11 951 961 11448771
- Caneparo L Huang YL Staudt N Tada M Ahrendt R Kazanskaya O Dickkopf-1 regulates gastrulation movements by coordinated modulation of Wnt/beta catenin and Wnt/PCP activities, through interaction with the Dally-like homolog Knypek Genes Dev 2007 21 465 480 17322405 PMC1804334
- Boutros M Paricio N Strutt DI Mlodzik M Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling Cell 1998 94 109 118 9674432
- Yamanaka H Moriguchi T Masuyama N Kusakabe M Hanafusa H Takada R JNK functions in the non-canonical Wnt pathway to regulate convergent extension movements in vertebrates EMBO Rep 2002 3 69 75 11751577 PMC1083927
- Pandur P Lasche M Eisenberg LM Kuhl M Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis Nature 2002 418 636 641 12167861
- Checler F Dunys J Pardossi-Piquard R Alves da Costa C p53 is regulated by and regulates members of the gamma-secretase complex Neurodegener Dis 2010 7 50 55 20160459
- MacGibbon GA Lawlor PA Walton M Sirimanne E Faull RL Synek B Expression of Fos, Jun, and Krox family proteins in Alzheimer's disease Exp Neurol 1997 147 316 332 9344557
- Gomez Ravetti M Rosso OA Berretta R Moscato P Uncovering molecular biomarkers that correlate cognitive decline with the changes of hippocampus' gene expression profiles in Alzheimer's disease PLoS One 2010 5 e10153 20405009 PMC2854141
- Criswell T Beman M Araki S Leskov K Cataldo E Mayo LD Delayed activation of insulin-like growth factor-1 receptor/Src/MAPK/Egr-1 signaling regulates clusterin expression, a pro-survival factor J Biol Chem 2005 280 14212 14221 15689620
- Tolias KF Duman JG Um K Control of synapse development and plasticity by Rho GTPase regulatory proteins Prog Neurobiol 2011 94 133 148 21530608 PMC3129138
- Montcouquiol M Crenshaw EB Kelley MW Noncanonical Wnt signaling and neural polarity Annu Rev Neurosci 2006 29 363 386 16776590
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- Authors
- Killick, R., Ribe, E. M., Al-Shawi, R., Malik, B., Hooper, C., Fernandes, C., Dobson, R., Nolan, P. M., Lourdusamy, A., Furney, S., Lin, K., Breen, G., Wroe, R., To, A. W. M., Leroy, K., Causevic, M., Usardi, A., Robinson, M., Noble, W., Williamson, R., Lunnon, K., Kellie, S., Reynolds, C. H., Bazenet, C., Hodges, A., Brion, J.-P., Stephenson, J., Paul Simons, J., & Lovestone, S.
- Affiliations
- King's College London (GB)
- Mary Lyon Centre at MRC Harwell (GB)
- Université Libre de Bruxelles (BE)
- University College London (GB)
- The University of Queensland (AU)
- Corresponding author
- Killick, R
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2012-11-20
- Volume
- 19
- Issue
- 1
- Pages
- 88-98
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3873038
- OpenAlex
- W2046422248
- Cited by
- 222
- References
- 5
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 13 · 2023: 20 · 2022: 20 · 2021: 18 · 2020: 23 · 2019: 24 · 2018: 12 · 2017: 20 · 2016: 14 · 2015: 13 · 2014: 16 · 2013: 11
- FWCI
- 8.05
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by-nc-nd)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by-nc-nd)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion)
- Open Research Exeter (University of Exeter) (submittedVersion, cc-by-nc-nd)
- Funders
- South London and Maudsley NHS Foundation Trust
- Wellcome Trust
- Royal Free London NHS Foundation Trust
- Alzheimer's Society
- National Institute for Health and Care Research (NF-SI-0512-10053)
- Bupa Foundation
- Astellas Pharma
- Astellas Pharma Europe
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Oncology › Clusterin in disease pathology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- clusterin, amyloid-beta, DKK1, Alzheimer's disease, Wnt signaling, planar cell polarity, JNK signaling, p53, neurotoxicity, tau phosphorylation, EGR1, Nab2, KLF10, cognitive impairment, transgenic mouse model, frontotemporal dementia
- MeSH terms
- Aged, Alzheimer Disease, Animals, Cells, Cultured, Embryo, Mammalian, Enzyme Inhibitors, Female, Gene Expression Regulation, Humans, Male, Mice, Inbred C57BL, Neurons, Amyloid beta-Peptides, Rats, Sprague-Dawley, MAP Kinase Signaling System, Intercellular Signaling Peptides and Proteins, Clusterin, Wnt Proteins, Mice, Rats
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