Cited by 201Alzheimer's disease research and treatmentsProtein Kinase Regulation and GTPase SignalingDementia and Cognitive Impairment Research

The DOI matches its Crossref record.

In Vitro Phosphorylation of the Cytoplasmic Domain of the Amyloid Precursor Protein by Glycogen Synthase Kinase‐3β

Aplin, Andrew E., Gibb, Graham M., Jacobsen, J. Steven, Gallo, Jean‐Marc, Anderton, Brian H.·1996·Journal of Neurochemistry

DOI 10.1046/j.1471-4159.1996.67020699.x

Open this paper in CoChat — free account

Abstract

The two pathological lesions found in the brains of Alzheimer's disease patients, neurofibrillary tangles and neuritic plaques, are likely to be formed through a common pathway. Neurofibrillary tangles are intracellular aggregates of paired helical filaments, the main component of which is hyperphosphorylated forms of the microtubule-associated protein tau. Extracellular neuritic plaques and diffuse and vascular amyloid deposits are aggregates of beta-amyloid protein, a 4-kDa protein derived from the amyloid precursor protein (APP). Using conditions in vitro under which two proline-directed protein kinases, glycogen synthase kinase-3beta (GSK-3beta) and mitogen-activated protein kinase (MAPK), were able to hyperphosphorylate tau, GSK-3beta but not MAPK phosphorylated recombinant APPcyt. The sole site of phosphorylation in APPcyt by GSK-3beta was determined by phosphoamino acid analysis and phosphorylation of APPcyt mutant peptides to be Thr743 (numbering as for APP770). This site was confirmed by endoproteinase Glu-C digestion of APPcyt and peptide sequencing. The ability of GSK-3beta to phosphorylate APPcyt and tau provides a putative link between the two lesions and indicates a critical role of GSK-3beta in the pathogenesis of Alzheimer's disease.

Integrity signals

Registry

Crossref · 10.1046/j.1471-4159.1996.67020699.x

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Sorted by citations

Items 101–200 of 201

The rise and fall of insulin signaling in Alzheimer’s disease
Chami, B., Steel, A. J., de la Monte, S. M., & Sutherland, G. T. (2016) · Metabolic Brain Disease · doi:10.1007/s11011-016-9806-1 · Cited by 48
Constitutively Active Glycogen Synthase Kinase-3β Gene Transfer Sustains Apoptosis, Inhibits Proliferation of Vascular Smooth Muscle Cells, and Reduces Neointima Formation After Balloon Injury in Rats
Park, K. W., Yang, H., Youn, S., Yang, H.-J., Chae, I., Oh, B., Lee, M. M., Park, Y.-B., Choi, Y. S., Kim, H.-S., et al. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000081633.53390.b4 · Cited by 49
Caspase-8, association with Alzheimer’s Disease and functional analysis of rare variants
Rehker, J., Rodhe, J., Nesbitt, R., Boyle, E. A., Martin, B., Lord, J., Karaca, I., Naj, A. C., Jessen, F., Helisalmi, S., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0185777 · Cited by 51
Silibinin Ameliorates Formaldehyde‐Induced Cognitive Impairment by Inhibiting Oxidative Stress
Wei, P., Li, X., Wang, S., Dong, Y., Yin, H., Gu, Z., Na, X., Wei, X., Yuan, J., Cao, J., et al. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/5981353 · Cited by 46
“Tau is hyperphosphorylated at more than 38 different sites, which interferes with the affinity of tau microtubule binding [45] and causes neurofibrillary tangle formation [46].”
Lithium Chloride Increases the Production of Amyloid-β Peptide Independently from Its Inhibition of Glycogen Synthase Kinase 3
Feyt, C., Kienlen‐Campard, P., Leroy, K., N’Kuli, F., Courtoy, P. J., Brion, J., & Octave, J. N. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501610200 · Cited by 46
Potential Implications of miRNAs in the Pathogenesis, Diagnosis, and Therapeutics of Alzheimer’s Disease
Wang, L., Shui, X., Diao, Y., Chen, D., Zhou, Y., & Lee, T. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216259 · Cited by 49
“GSK-3 β is a kinase that is responsible for the Thr668 phosphorylation of APP [159,160].”
Background
Amyloid β Protein Precursor Is Phosphorylated by JNK-1 Independent of, yet Facilitated by, JNK-Interacting Protein (JIP)-1
Scheinfeld, M. H., Ghersi, E., Davies, P., & D'adamio, L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304853200 · Cited by 47
Facilitation of Stress-induced Phosphorylation of β-Amyloid Precursor Protein Family Members by X11-like/Mint2 Protein
Taru, H., & Suzuki, T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312007200 · Cited by 44
The multifaceted role of WNT signaling in Alzheimer’s disease onset and age-related progression.
Kostes, W. W., & Brafman, D. A. (2023) · Cells · doi:10.3390/cells12081204 · Cited by 43
“The same study also showed inhibition of the JNK pathway reduced Aβ deposition in neurons by shifting APP processing to the non-amyloidogenic pathway [231].”
BackgroundInfluential
Aberrant Expression of RCAN1 in Alzheimer’s Pathogenesis: A New Molecular Mechanism and a Novel Drug Target
Wu, Y., Ly, P. T. T., & Song, W. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8704-y · Cited by 40
“Moreover, GSK3β is also actively involved in APP phosphorylation which potentiates Aβ generation [160, 161].”
Regulation of FE65 Nuclear Translocation and Function by Amyloid β-Protein Precursor in Osmotically Stressed Cells
Nakaya, T., Kawai, T., & Suzuki, T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801827200 · Cited by 41
Molecular mechanisms and therapeutic potential of lithium in Alzheimer’s disease: repurposing an old class of drugs
Shen, Y., Zhao, M., Zhao, P., Meng, L., Zhang, Y., Zhang, G., Taishi, Y., & Sun, L. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1408462 · Cited by 45
In AβPP‐overexpressing cultured human muscle fibers proteasome inhibition enhances phosphorylation of AβPP751 and GSK3β activation: effects mitigated by lithium and apparently relevant to sporadic inclusion‐body myositis
Terracciano, C., Nogalska, A., Engel, W. K., & Askanas, V. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06461.x · Cited by 38
Lithium Attenuates Scopolamine-Induced Memory Deficits with Inhibition of GSK-3β and Preservation of Postsynaptic Components
Wu, Y., Wang, X., Tan, L., Liu, D., Liu, X.-H., Wang, Q., Wang, J., & Zhu, L. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130521 · Cited by 37
“Previous studies have demonstrated that activation of GSK-3 plays a critical role in AD-like tau hyperphosphorylation, amyloid- accumulation, and synapse and memory deficits [47–49].”
Amyloid Precursor Protein Enhances Nav1.6 Sodium Channel Cell Surface Expression
Liu, C., Tan, F. C. K., Xiao, Z., & Dawe, G. S. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.617092 · Cited by 37
Multiple Immunostaining Methods to Detect Traumatic Axonal Injury in the Rat Fluid-Percussion Brain Injury Model
HOSHINO, S., Kobayashi, S., Furukawa, T., Asakura, T., & Teramoto, A. (2003) · Neurologia medico-chirurgica · doi:10.2176/nmc.43.165 · Cited by 35
Signal Transduction Therapeutics: Relevance for Alzheimer's Disease
Silva, O. A. B. D. C. E., Fardilha, M., Henriques, A. G., Rebelo, S., Vieira, S. I., & Silva, E. F. D. C. E. (2004) · Journal of Molecular Neuroscience · doi:10.1385/jmn:23:1-2:123 · Cited by 34
Role of P2X7 and P2Y 2 receptors on α-secretase-dependent APP processing: Control of amyloid plaques formation “ in vivo ” by P2X7 receptor
Miras‐Portugal, M. T., Díaz‐Hernandéz, J. I., Gómez‐Villafuertes, R., Dı́az-Hernández, M., Artalejo, A. R., & Gualix, J. (2015) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2015.02.005 · Cited by 33
“It has been reported that an increase in GSK-3 activity [18] correlates with the phosphorylation of APP intracellular domain, making it a more suitable substrate for γ-secretase proteolysis, which enhances Aβ-42 production [19].”
Background
Exercise training and BDNF injections alter amyloid precursor protein (APP) processing enzymes and improve cognition
Baranowski, B. J., Mohammad, A., Finch, M. S., Brown, A. D. H., Dhaliwal, R., Marko, D. M., LeBlanc, P. J., McCormick, C. M., Fajardo, V. A., & MacPherson, R. E. K. (2023) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00114.2023 · Cited by 36
GSAP regulates lipid homeostasis and mitochondrial function associated with Alzheimer’s disease
Xu, P., Chang, J. C., Zhou, X., Wang, W., Bamkole, M. A., Wong, E., Bettayeb, K., Jiang, L.-L., Huang, T. Y., Luo, W., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20202446 · Cited by 36
“Thr668 of APP can be phosphorylated by several kinases to regulate a variety of APP functions (Aplin et al., 1996; Iijima et al., 2000; Standen et al., 2001; Suzuki et al., 1994).”
Background
Neuroprotective Effect of SLM, a Novel Carbazole-Based Fluorophore, on SH-SY5Y Cell Model and 3xTg-AD Mouse Model of Alzheimer’s Disease
Wu, X., Kosaraju, J., Zhou, W., & Tam, K. Y. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6b00388 · Cited by 28
Phosphorylation of amyloid precursor protein (APP) at Tyr687 regulates APP processing by α- and γ-secretase
Takahashi, K., Niidome, T., Akaike, A., et al. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.10.013 · Cited by 27
Glycogen Synthase Kinase-3.BETA.2 Has Lower Phosphorylation Activity to Tau than Glycogen Synthase Kinase-3.BETA.1
Saeki, K., Machida, M., Kinoshita, Y., Takasawa, R., & Tanuma, S. (2011) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.34.146 · Cited by 25
Atorvastatin ameliorates cognitive impairment, Aβ1-42 production and Tau hyperphosphorylation in APP/PS1 transgenic mice
Zhou, D., Liu, H., Li, C., Wang, F., Shi, Y., Liu, L., Zhao, X., Liu, A., Zhang, J., Wang, C., et al. (2016) · Metabolic Brain Disease · doi:10.1007/s11011-016-9803-4 · Cited by 26
Phosphorylation of kinase-related protein (telokin) in tonic and phasic smooth muscles
Krymsky, M. A., Kudryashov, D. S., Shirinsky, V. P., et al. (2001) · Journal of Muscle Research and Cell Motility · doi:10.1023/a:1014503604270 · Cited by 25
Advances in quantitative structure–activity relationship models of anti-Alzheimer’s agents
Ambure, P. S., & Roy, K. (2014) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2014.909404 · Cited by 24
“Glycogen synthase kinase-3a (GSK3a) was found to be an attractive target for the treatment of AD, due to its dual action in the formation of both amyloid plaques and neurofibrillary tangles [82].”
Background
Diabetes, Insulin and Alzheimer's Disease
Craft, S., & Christen, Y. (2010) · Research and perspectives in Alzheimer's disease · doi:10.1007/978-3-642-04300-0 · Cited by 24
Amyloid precursor protein modulates Nav1.6 sodium channel currents through a Go-coupled JNK pathway
Li, S., Wang, X., Ma, Q., Yang, W.-L., Zhang, X., Dawe, G. S., & Xiao, Z. (2016) · Scientific Reports · doi:10.1038/srep39320 · Cited by 24
The Y682ENPTY687 motif of APP: Progress and insights toward a targeted therapy for Alzheimer’s disease patients
Matrone, C., Iannuzzi, F., & Annunziato, L. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.04.003 · Cited by 24
Silencing I2PP2A Rescues Tau Pathologies and Memory Deficits through Rescuing PP2A and Inhibiting GSK-3β Signaling in Human Tau Transgenic Mice
Zhang, Y., Ma, R.-H., Li, X., Zhang, J.-Y., Shi, H.-R., Wei, W., Luo, D., Wang, Q., Wang, J., & Liu, G. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00123 · Cited by 23
GSK-3β : une kinase au cœur des maladies neuro-dégénératives ?
Petit-Paitel, A. (2010) · médecine/sciences · doi:10.1051/medsci/2010265516 · Cited by 22
Ca 2+ ‐dependent release of ATP from astrocytes affects herpes simplex virus type 1 infection of neurons
Puma, D. D. L., Marcocci, M. E., Lazzarino, G., Chiara, G. D., Tavazzi, B., Palamara, A. T., Piacentini, R., & Grassi, C. (2020) · Glia · doi:10.1002/glia.23895 · Cited by 22
P2X7 Receptor: an Emerging Target in Alzheimer’s Disease
Huang, Q., Ying, J., Yu, W., Dong, Y., Xiong, H., Zhang, Y., Liu, J., Wang, X., & Hua, F. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03699-9 · Cited by 26
Transthyretin Suppresses Amyloid-β Secretion by Interfering with Processing of the Amyloid-β Protein Precursor
Li, X., Song, Y., Sanders, C. R., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160033 · Cited by 19
Phosphorylation of β-amyloid precursor protein (APP) cytoplasmic tail facilitates amyloidogenic processing during apoptosis
Sodhi, C. P., Perez, R. G., & Gottardi-Littell, N. R. (2008) · Brain Research · doi:10.1016/j.brainres.2008.01.031 · Cited by 19
“Several protein kinases previously have been demonstrated to phosphorylate T668, including GSK3β (Aplin et al., 1996), JNK3 (Kimberly et al., 2005; Standen et al., 2001), and the cyclin-dependent kinases cdc2 (Suzuki et al., 1994) and cdk5 (Iijima et al., 2000); these protein kinases functionally have been implicated…”
Atlas stumbled: Kinesin light chain‐1 variant E triggers a vicious cycle of axonal transport disruption and amyloid‐β generation in Alzheimer's disease
Gan, K. J., Morihara, T., & Silverman, M. A. (2014) · BioEssays · doi:10.1002/bies.201400131 · Cited by 17
“Furthermore, the APP intracellular domain (AICD) is a substrate for GSK3b in vitro and in vivo [96, 97].”
Background
Inhibition of neuronal calcium oscillations by cell surface APP phosphorylated on T668
Santos, S. F., Tasiaux, B., Sindic, C., & Octave, J. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.01.006 · Cited by 17
Potassium 2-(1-Hydroxypentyl)-Benzoate Improves Memory Deficits and Attenuates Amyloid and τ Pathologies in a Mouse Model of Alzheimer's Disease
Peng, Y., Hu, Y., Xu, S., Rong, X., Li, J., Li, P., Wang, L., Yang, J., & Wang, X. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.213140 · Cited by 16
The link between sarcopenic obesity and Alzheimer's disease: a brain‐derived neurotrophic factor point of view
Copeland, E. N., LeBlanc, P. J., Duarte‐Guterman, P., Fajardo, V. A., & MacPherson, R. E. K. (2025) · The Journal of Physiology · doi:10.1113/jp288032 · Cited by 16
“Further, BDNF has been shown to regulate β -site amyloid precursor protein cleaving enzyme-1 (BACE1) activity, the rate-limiting enzyme in amyloidogenic APP processing.”
Influential
Identification of potential therapeutic and diagnostic characteristics of Alzheimer disease by targeting the miR-132-3p/FOXO3a-PPM1F axis in APP/PS1 mice
Fu, X., Liu, J., Xie, J., Chen, G., Zhang, H., Meng, F., Wu, M., Li, Q., Liu, Y., Wang, W., et al. (2022) · Brain Research · doi:10.1016/j.brainres.2022.147983 · Cited by 13
Midbrain degeneration triggers astrocyte reactivity and tau pathology in experimental Alzheimer’s Disease
Barbera, L. L., Krashia, P., Loffredo, G., Cauzzi, E., Paolis, M. L. D., Montanari, M., Saba, L., Spoleti, E., Ficchì, S., Zaccone, C., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00893-2 · Cited by 17
Reduced amyloidogenic processing of the amyloid β-protein precursor by the small-molecule Differentiation Inducing Factor-1
Myre, M. A., Washicosky, K. J., Moir, R. D., Tesco, G., Tanzi, R. E., & Wasco, W. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.12.008 · Cited by 13
Pin1 Modulation in Physiological Status and Neurodegeneration. Any Contribution to the Pathogenesis of Type 3 Diabetes?
Bianchi, M., & Manco, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082319 · Cited by 13
“Alternatively, Pin1 may modulate APP processing to inhibit the phosphorylation of Thr668-Pro motif of APP performed by GSK-3β [73,76] Processing was observed in Pin1 WT or KD cells transfected both with WT or the mutated T330A GSK-3β constructs [73].”
Background
Extensive nuclear sphere generation in the human Alzheimer's brain
Kolbe, K., Bukhari, H., Looße, C., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.08.016 · Cited by 12
Examination of Akt and GSK3β in BDNF ‐mediated reductions in BACE1 activity in neuronal cells
Baranowski, B. J., Mohammad, A., LeBlanc, P. J., Fajardo, V. A., & MacPherson, R. E. K. (2024) · Physiological Reports · doi:10.14814/phy2.70001 · Cited by 10
“Active GSK3 β phosphorylates APP at the Thr 668 site, resulting in the precursor protein having a higher affinity to BACE1 cleavage (Aplin et al., 1996; Griffin et al., 2005; Hetman et al., 2000; Ly et al., 2013).”
Background
Alzheimer’s Disease: A Review of Molecular Mechanisms and Therapeutic Implications by Targeting Sirtuins, Caspases, and GSK-3
Pandya, K., Roul, K., Tripathi, A., Belemkar, S., Sinha, A., Erol, M., & Kumar, D. (2025) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5c00207 · Cited by 11
Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach
Haut, F., Argyrousi, E. K., & Arancio, O. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010259 · Cited by 11
“Interestingly, in a study by Aplin et al., it was shown that GSK3 β could phosphorylate AICD/AID at the T688 residue that is implicated in the development of AD [53].”
Background
Mechanisms of tauopathies
Froelich-Fabre, S., & Bhat, R. V. (2004) · Drug Discovery Today Disease Mechanisms · doi:10.1016/j.ddmec.2004.11.012 · Cited by 10
Recent Advances in Computational Approaches for Designing Potential Anti-Alzheimer’s Agents
Gómez‐Ganau, S., de Julián‐Ortiz, J. V., & Gozalbes, R. (2017) · Neuromethods · doi:10.1007/978-1-4939-7404-7_2 · Cited by 9
Testing Fmr1KO Phenotypes in Response to GSK3 Inhibitors: SB216763 versus AFC03127
Westmark, P. R., Garrone, B., Ombrato, R., Milanese, C., Giorgio, F. P. D., & Westmark, C. J. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.751307 · Cited by 9
“GSK3 mediates phosphorylation of the cytoplasmic domain of APP and processing of APP to amyloid-beta (Aβ; Aplin et al., 1996; Phiel et al., 2003; Su et al., 2004).”
Background
Roles of Glycogen Synthase Kinase-3 in Alzheimer's Disease: From Pathology to Treatment Target
Liu, H., Leu, S., & Chuang, D. (2012) · Journal of Experimental & Clinical Medicine · doi:10.1016/j.jecm.2012.04.001 · Cited by 9
2-Deoxyglucose induces β-APP overexpression, tau hyperphosphorylation and expansion of the trans-part of the Golgi complex in rat cerebral cortex
Grieb, P., Gordon‐Krajcer, W., Frontczak‐Baniewicz, M., Walski, M., Ryba, M., Kryczka, T., Fiedorowicz, M., Kulinowski, P., Sułek, Z., Majcher, K., et al. (2004) · Acta Neurobiologiae Experimentalis · doi:10.55782/ane-2004-1533 · Cited by 8
Glycogen synthase kinase 3β (GSK3β) and presenilin (PS) are key regulators of kinesin-1-mediated cargo motility within axons
Banerjee, R., & Gunawardena, S. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1202307 · Cited by 7
“APP can be phosphorylated at T668 by GSK3β (Aplin et al., 1996) in addition to Cdk5 (Iijima et al.”
Background
Role of Glycogen Synthase Kinase-3β in APP Hyperphosphorylation Induced by NMDA Stimulation in Cortical Neurons
Ploia, C., Sclip, A., Colombo, A. V., Repici, M., Gardoni, F., Luca, M. D., Forloni, G., Antoniou, X., & Borsello, T. (2010) · Pharmaceuticals · doi:10.3390/ph3010042 · Cited by 7
“We investigated the impact of an excitotoxic stimulus such as NMDA on the phosphorylation of APP and on the activation of the three kinases that are involved in this phosphorylation, namely: JNK [6,17], Cdk5 [5,7] and GSK-3β [4].”
Background
Links Between Amyloid and Tau Biology in Alzheimer’s Disease and Their Cholinergic Aspects
Siegel, G. J., Chauhan, N. B., & Karczma, A. G. (2007) · Springer eBooks · doi:10.1007/978-0-387-46526-5_10 · Cited by 6
The Role of Glycogen Synthase Kinase-3 (GSK-3) in Alzheimer’s Disease
Medina, M., & Avil, J. (2011) · InTech eBooks · doi:10.5772/16879 · Cited by 7
“Furthermore, APP has also been shown to be a substrate for GSK-3 in vitro (Aplin et al., 1996) and in vivo (Rockenstein et al., 2007), suggesting a role of GSK-3 in APP transport and maturation (da Cruz e Silva & da Cruz e Silva, 2003; Lee et al., 2003) from the early secretory pathway through the…”
Background
N-terminal phosphorylation regulates the activity of glycogen synthase kinase 3 from Plasmodium falciparum
Pažický, S., Alder, A., Mertens, H. D. T., Svergun, D. I., Gilberger, T., & Löw, C. (2022) · Biochemical Journal · doi:10.1042/bcj20210829 · Cited by 6
Flavonoids and fibrate modulate apoE4-induced processing of amyloid precursor protein in neuroblastoma cells
Davra, V., & Benzeroual, K. E. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1245895 · Cited by 5
Glycogen Synthase Kinase-3
Woodgett, J. R. (2013) · Encyclopedia of Biological Chemistry · doi:10.1016/b978-0-12-378630-2.00459-x · Cited by 5
GSK-3: An “Ace” Among Kinases
Mathuram, T. L. (2024) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1089/cbr.2024.0025 · Cited by 4
Beta-Secretase 1 Recruits Amyloid-Beta Precursor Protein to ROCK2 Kinase, Resulting in Erroneous Phosphorylation and Beta-Amyloid Plaque Formation
Hajdú, I., Végh, B. M., Szilágyi, A., & Závodszky, P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310416 · Cited by 4
Flavonoid-Based Derivatives for Modulating Various Targets of Alzheimer’s Disease
Pandey, J. (2023) · Springer eBooks · doi:10.1007/978-981-99-6038-5_11 · Cited by 3
Effect of Lithium Drug on Binding Affinities of Glycogen Synthase Kinase-3 β to Its Network Partners: A New Computational Approach
Rouhani, M., & Hadi‐Alijanvand, H. (2021) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.1c00952 · Cited by 3
Is Alzheimer’s a Disorder of Ageing and Why Don’t Mice get it? The Centrality of Insulin Signalling to Alzheimer’s Disease Pathology
Lovestone, S., & Killick, R. (2010) · Research and perspectives in Alzheimer's disease · doi:10.1007/978-3-642-04300-0_9 · Cited by 3
The γ-Secretase Protease Complexes in Neurodegeneration, Cancer and Immunity
Coleman-Vaughan, C., Mal, A., De, A., & McCarthy, J. V. (2017) · Springer eBooks · doi:10.1007/978-981-10-6141-7_3 · Cited by 2
Pathogenesis of Sporadic Inclusion‐Body Myositis: Role of Aging and Muscle‐Fiber Degeneration, and Accumulation of the Same Proteins as in Alzheimer and Parkinson Brains
Askanas, V., Engel, W. K., & Nogalska, A. (2011) · Wiley eBooks · doi:10.1002/9781444398311.ch7 · Cited by 2
Dementia: The Significance of Cerebral Metabolic Disturbances in Alzheimer's Disease. Relation to Parkinson's Disease
Hoyer, S., & Frölich, L. (2007) · Springer eBooks · doi:10.1007/978-0-387-30377-2_12 · Cited by 2
Therapeutic targeting of glycogen synthase kinase-3: Strategy to address neurodegenerative diseases
Noor, S., Raza, A., & Hassan, M. I. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91287-7.00008-9 · Cited by 1
Proteolytic processing of the Alzheimer APP protein family during neuronal differentiation
Holback, S. (2009) · KTH Publication Database DiVA (KTH Royal Institute of Technology) · Cited by 1
Beyond Phosphate Esters: Synthesis of Unusually Phosphorylated Peptides and Proteins for Proteomic Research
Hauser, A., Stieger, C. E., & Hackenberger, C. P. R. (2021) · doi:10.1002/9783527823567.ch20 · Cited by 1
Regulation of neuritogenesis in neuroblastoma cells by components of the WNT signalling pathway.
Orme, M. H. (2002) · OpenGrey (Institut de l'Information Scientifique et Technique)
Targets and Small Molecules Against Tauopathies. Part 1: From Genes to Soluble, Aggregation-Prone Tau Proteins
Seneci, P. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-803959-5.50015-5
α-Secretase processing of the Alzheimer amyloid-β precursor protein and its homolog APLP2
Jacobsen, K. T. (2013) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Lítio e expressão gênica: implicações para a doença de Alzheimer.
Mendes, C. T. (2008) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.87.2008.tde-10032009-113854
Cooperative calcium and zinc signaling underlies oxidantinduced neuronal injury
McCord, M. C. (2013) · D-Scholarship@Pitt (University of Pittsburgh)
In vitro modelling of tau phosphorylating kinases : emphasis of Cdk5
Jämsä, A. (2007) · Figshare
Flavonoids as Modulators of Amyloid Precursor Protein Metabolism and Alzheimer Disease Pathology
Rezai-Zadeh, K. P. (2008) · Digital Commons - University of South Florida (University of South Florida)
The Effect of Acute LPS-Induced Immune Activation and Brain Insulin Signaling Disruption in a Diabetic Model of Alzheimer's Disease
Murtishaw, A. S. (2020) · Digital Scholarship - UNLV (University of Nevada Reno) · doi:10.34917/6456429
NEURODEGENERATIVE DISEASES AND TAU: PATHOLOGICAL EVENTS AND MOLECULAR TARGETS
Seneci, P. (2012) · Istituto Lombardo - Accademia di Scienze e Lettere - Rendiconti di Scienze · doi:10.4081/scie.2012.136
GSK-3b : une kinase au cœur des maladies neuro-?
Petit-Paitel, A. (2010)
RetinoicAcidAttenuates-AmyloidDepositionandRescues MemoryDeficitsinanAlzheimer'sDiseaseTransgenic MouseModel
ShawnGoodwin, J. (2008)
Using TUDCA to treat Alzheimer's disease after pathology onset in APP/PS1 mice
Dionísio, P. (2014) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Mass Spectrometry-Based Investigation of APP-Dependent Mechanisms in Neurodegeneration
Chaput, D. (2015) · Digital Commons - University of South Florida (University of South Florida)
Using TUDCA to treat Alzheimer's disease after pathology onset in APP/PS1 mice
Farmácia, F. D. (2014)
Efectos del envejecimiento y la neurodegeneración sobre la plasticidad neuronal en el hipocampo
Morgenstern, N. A. (2011) · Repositorio Digital Institucional de la Universidad de Buenos Aires (Universidad de Buenos Aires)
Beneficial effects of quetiapine in the APP/PS1 transgenic mice: implications for early intervention for Alzheimer's disease
Zhu, S. (2011) · Mspace (University of Manitoba)
N-terminal phosphorylation regulates the activity of Glycogen Synthase Kinase 3 from Plasmodium falciparumPreprint
Pažický, S., Alder, A., Mertens, H. D. T., Svergun, D. I., Gilberger, T., & Löw, C. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.18.448949
Studies on Relationship between a Microtubule-associated Protein Tau and Alzheimer's Disease Progression and Drug Discovery Targeting Tau
大西, 智., & Onishi, T. (2016) · Terrestrial Environment Research Center (University of Tsukuba)
Chapter 4. Transgenic Mice Overexpressing GSK-3β as Animal Models for Alzheimer's Disease
Hernández, F. (2011) · Royal Society of Chemistry eBooks · doi:10.1039/9781849732758-00052
Effects of inhibition of glycogen synthase kinase 3p on neuromuscular synaptic transmission in transgenic mice with model of alzheimer's disease
Mukhamedyarov, M. A., Grigoryev, P. N., Asgatovna, U. E., & Zefirov, A. L. (2020) · Genes and Cells · doi:10.23868/202012009
Understanding the Potential Targets of Alzheimer’s Disease
Varshini, M. S., Krishnamurthy, P. T., Chintamaneni, P. K., & Reddy, R. A. (2024) · Springer eBooks · doi:10.1007/978-981-96-0259-9_15
Elevated BACE1 mRNA Level is Associated with Lower miR-15a-5p and miR-19b-3p Expressions in Peripheral Blood Mononuclear Cells of Patients with Late-Onset Alzheimer’s Disease: Wet Lab Results and Bioinformatics Analysis
Rasadi, A., Sasani, S. T., & Ajamian, F. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05159-y
“The serine/threonine kinases GSK-3β and CDK5 can phosphorylate APP at the T668 residue [59–62], a process upregulated in the hippocampus of AD patients and associated with BACE1-mediated cleavage [63].”
eIF2Bε phosphorylation activates integrated stress response-mediated protein translation and links stress signalling to amyloidogenesis in Alzheimer’s diseasePreprint
Fanlo-Ucar, H., Planas-Clopes, C., Bagudanch, O., Pardo, C., Troncoso-Cotal, S., Alvarez, A. R., Oliva, B., & Muñoz, F. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.03.686297
“42,43 While GSK-3β induces Aβ 1-42 generation by increasing BACE1 transcription, 27 indirectly enhancing γ -secretase activity, 44 and phosphorylating APP and increasing its processing , 45,46 no modulation of BACE1 translation by GSK-3β has been established yet.”
Aβ Modulates Extracellular Vesicles Proteomic Profile Impacting Phosphorylation Mediators
Vaz, M., Martins, T. S., Trigo, D., Silva, O. A. B. D. C. E., Amado, F. M. L., Vitorino, R. M. P., & Henriques, A. G. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05343-0 · Cited by 1
“Additionally, GSK3β can also phosphorylate APP [77, 78, 114].”
Chromosome Missegregation in Alzheimer's Disease Caused by Presenilin 1
Boeras, D. I. (2005) · Digital Commons - University of South Florida (University of South Florida)
Detection of the Alzheimer's disease soluble amyloid precursor protein and modulation of its proteolytic processing
Taverna, M. (2014) · Electronic Theses of LMU Munich (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.17796
The Emphatic Role of Mitogen-Activated Protein Kinases (MAPKs) in the Cellular Mechanisms Mediating Alzheimer's Disease
Haddad, J. J. (2007) · Technische Universität Dortmund Eldorado (Technische Universität Dortmund) · doi:10.17877/de290r-7331
“transfection with GSK-3α or GSK-3β decreased the electrophoretic mobility of Tau so that it resembled that of PHF-Tau, and induced reactivity with PHFTau-selective monoclonal antibodies (Aplin et al., 1996; Lovestone et al., 1994).”
BackgroundMethod
Étude de la régulation endogène de la voie de signalisation calcineurine-NFAT et de son rôle dans la toxicité induite par les inhibiteurs pharmacologiques de la calcineurine après transplantation
Lena, C. (2016) · theses.fr (ABES) · doi:10.70675/5307b907z0301z47e0z8d12z4ee93bd791f7
The emerging role of polo-like kinase 2 in Alzheimer's disease
Martínez-Drudis, L., Sheta, R., Musiol, D., Teixeira, M., & Oueslati, A. (2026) · Experimental Neurology · doi:10.1016/j.expneurol.2026.115806
Current Landscape of Glycogen Synthase Kinase-3β PET Tracers: Progress, Limitations, and Perspectives—A Narrative Review
Chen, H., Zhang, L., Jiao, B., Sun, X., Guan, L., Niu, R., Li, B., Jiang, X., & Wu, Z. (2026) · Pharmaceuticals · doi:10.3390/ph19091457

Authors: Aplin, A. E., Gibb, G. M., Jacobsen, J. S., Gallo, J., & Anderton, B. H.
Corresponding author: Aplin, Andrew E.
ORCID: Aplin, Andrew E.
Gallo, Jean‐Marc
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 1996-08
Volume: 67
Issue: 2
Pages: 699-707
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1046/j.1471-4159.1996.67020699.x
OpenAlex: W2069584842
Cited by: 201
References: 0
Citations by year: 2026: 2 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 4 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 11 · 2016: 10 · 2015: 7 · 2014: 13 · 2013: 6 · 2012: 7
FWCI: 1.35
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2305 d)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: amyloid precursor protein, glycogen synthase kinase-3β, protein phosphorylation, Alzheimer's disease, tau hyperphosphorylation, neurofibrillary tangles, neuritic plaques, amyloid-beta, mitogen-activated protein kinase, phosphorylation site mapping
MeSH terms: Amino Acid Sequence, Animals, Base Sequence, Cytoplasm, Humans, Molecular Sequence Data, Phosphorylation, Phosphothreonine, Protein-Tyrosine Kinases, Amyloid beta-Protein Precursor, Calcium-Calmodulin-Dependent Protein Kinases, DNA Primers, Mitogen-Activated Protein Kinase 1, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

In Vitro Phosphorylation of the Cytoplasmic Domain of the Amyloid Precursor Protein by Glycogen Synthase Kinase‐3β

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cited by

Related

Metadata

Record

About these checks