Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer's disease
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It has been established for a long time that brain glucose metabolism is impaired in Alzheimer's disease. Recent studies have demonstrated that impaired brain glucose metabolism precedes the appearance of clinical symptoms, implying its active role in the development of Alzheimer's disease. However, the molecular mechanism by which this impairment contributes to the disease is not known. In this study, we demonstrated that protein O-GlcNAcylation, a common post-translational modification of nucleocytoplasmic proteins with beta-N-acetyl-glucosamine and a process regulated by glucose metabolism, was markedly decreased in Alzheimer's disease cerebrum. More importantly, the decrease in O-GlcNAc correlated negatively with phosphorylation at most phosphorylation sites of tau protein, which is known to play a crucial role in the neurofibrillary degeneration of Alzheimer's disease. We also found that hyperphosphorylated tau contained 4-fold less O-GlcNAc than non-hyperphosphorylated tau, demonstrating for the first time an inverse relationship between O-GlcNAcylation and phosphorylation of tau in the human brain. Downregulation of O-GlcNAcylation by knockdown of O-GlcNAc transferase with small hairpin RNA led to increased phosphorylation of tau in HEK-293 cells. Inhibition of the hexosamine biosynthesis pathway in rat brain resulted in decreased O-GlcNAcylation and increased phosphorylation of tau, which resembled changes of O-GlcNAcylation and phosphorylation of tau in rodent brains with decreased glucose metabolism induced by fasting, but not those in rat brains when protein phosphatase 2A was inhibited. Comparison of tau phosphorylation patterns under various conditions suggests that abnormal tau hyperphosphorylation in Alzheimer's disease brain may result from downregulation of both O-GlcNAcylation and protein phosphatase 2A. These findings suggest that impaired brain glucose metabolism leads to abnormal hyperphosphorylation of tau and neurofibrillary degeneration via downregulation of tau O-GlcNAcylation in Alzheimer's disease. Thus, restoration of brain tau O-GlcNAcylation and protein phosphatase 2A activity may offer promising therapeutic targets for treating Alzheimer's disease.
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O-GlcNAcylation negatively regulates tau phosphorylation.
“O-GlcNAcylation negatively regulates tau phosphorylation, as Ser and Thr targets for O-GlcNAcylation and phosphorylation overlap to some extent.”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [187]
Inhibition of O-GlcNAcase reduces tau phosphorylation.
“whereas inhibition of O-GlcNAcase reduces tau phosphorylation [187, 188].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [187]
Downregulation of O-GlcNAc transferase leads to reduced O-GlcNAcylation and increased tau phosphorylation.
“Downregulation of O-GlcNAc transferase leads to reduced O-GlcNAcylation and increased tau phosphorylation”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [187]
Decreased levels of O-GlcNAcylated tau have been observed in AD brain, and inversely correlates with tau phosphorylation at multiple sites.
“Decreased levels of O-GlcNAcylated tau have been observed in AD brain, and inversely correlates with tau phosphorylation at multiple sites”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [187]
In brain tissue from patients with AD compared with healthy elderly controls, levels of O-GlcNAcylated tau are reduced.
“In brain tissue from patients with AD, compared with healthy elderly controls, levels of O-GlcNAcylated tau are reduced40.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [40]
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Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., & Binder, L. I. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.13.4913 · Cited by 3,676 · see citing works
Self-citationConsortium to Establish a Registry for Alzheimer's Disease (CERAD)
Fillenbaum, G., & Heyman, A. (2002) · doi:10.1002/0470846410.ch42(iii · Cited by 2,859 · see citing works
Staging of alzheimer's disease-related neurofibrillary changes
Braak, H., & Braak, E. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00021-6 · Cited by 2,357 · see citing works
(1995) · PubMed Central · doi:10.2967/jnumed.120.252510a · Cited by 996 · see citing works
Alonso, A. D. C., Zaidi, T., Novák, M., Grundke, I., & Iqbal, K. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121119298 · Cited by 968 · see citing works
Self-citationLucas, J. J., Hernández, F., Gómez‐Ramos, P., Morán, M. A., Hen, R., & Avila, J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.1.27 · Cited by 903 · see citing works
Köpke, E., Tung, Y. C., Shaikh, S., Alonso, A. C., Iqbal, K., & Grundke-Iqbal, I. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80536-5 · Cited by 779 · see citing works
Self-citationO-GlcNAcylation regulates phosphorylation of tau: A mechanism involved in Alzheimer's disease
Liu, F., Iqbal, K., Grundke-Iqbal, I., Hart, G. W., & Gong, C.-X. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400348101 · Cited by 775 · see citing works
Self-citationLiu, F., Grundke‐Iqbal, I., Iqbal, K., & Gong, C. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04391.x · Cited by 759 · see citing works
Self-citationRole of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease.
Alonso, A. C., Zaidi, T., Grundke-Iqbal, I., & Iqbal, K. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.12.5562 · Cited by 738 · see citing works
Self-citationDEFECTIVE BRAIN MICROTUBULE ASSEMBLY IN ALZHEIMER'S DISEASE
Iqbal, K., Zaidi, T., Wen, G. Y., Grundke, I., MERZ, P. A., Shaikh, S., Wisniewski, H., Alafuzoff, I. I., & Winblad, B. G. (1986) · The Lancet · doi:10.1016/s0140-6736(86)92134-3 · Cited by 727 · see citing works
Self-citationGong, C., & Iqbal, K. (2008) · Current Medicinal Chemistry · doi:10.2174/092986708785909111 · Cited by 649 · see citing works
Self-citationde Leon, M. J., Convit, A., Wolf, O. T., Tarshish, C. Y., DeSanti, S., Rusinek, H., Tsui, W., Kandil, E., Scherer, A. J., Roche, A., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191044198 · Cited by 629 · see citing works
Drzezga, A., Lautenschlager, N., Siebner, H., Riemenschneider, M., Willoch, F., Minoshima, S., Schwaiger, M., & Kurz, A. (2003) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-003-1194-1 · Cited by 587 · see citing works
Phosphoprotein Phosphatase Activities in Alzheimer Disease Brain
Gong, C., Singh, T. J., Grundke‐Iqbal, I., & Iqbal, K. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03603.x · Cited by 527 · see citing works
Self-citationSimpson, I. A., Chundu, K. R., Davies‐Hill, T., Honer, W. G., & Davies, P. (1994) · Annals of Neurology · doi:10.1002/ana.410350507 · Cited by 490 · see citing works
Jackson, G. R., Wiedau-Pazos, M., Sang, T.-K., Wagle, N., Brown, C. A., Massachi, S., & Geschwind, D. H. (2002) · Neuron · doi:10.1016/s0896-6273(02)00706-7 · Cited by 488 · see citing works
(2013) · Acta Neurologica Belgica · doi:10.1007/13760.2240-2993 · Cited by 462 · see citing works
The Hexosamine Signaling Pathway: Deciphering the "O-GlcNAc Code"
Love, D. C., & Hanover, J. A. (2005) · Science s STKE · doi:10.1126/stke.3122005re13 · Cited by 462 · see citing works
Hanger, D. P., Byers, H. L., Wray, S., Leung, K.-Y., Saxton, M. J., Seereeram, A., Reynolds, C. H., Ward, M. A., & Anderton, B. H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703269200 · Cited by 455 · see citing works
Phosphatase Activity Toward Abnormally Phosphorylated τ: Decrease in Alzheimer Disease Brain
Gong, C., Shaikh, S., Wang, J., Zaidi, T., Grundke, I., & Iqbal, K. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65020732.x · Cited by 440 · see citing works
Self-citationPost-translational modifications of tau protein in Alzheimer’s disease
Gong, C.-X., Liu, F., Grundke-Iqbal, I., & Iqbal, K. (2005) · Journal of Neural Transmission · doi:10.1007/s00702-004-0221-0 · Cited by 437 · see citing works
Self-citationRegulation of a Cytosolic and Nuclear O-GlcNAc Transferase
Kreppel, L. K., & Hart, G. W. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.45.32015 · Cited by 425 · see citing works
Gong, C.-X., Lidsky, T., Wegiel, J., Zuck, L., Grundke-Iqbal, I., & Iqbal, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.8.5535 · Cited by 405 · see citing works
Self-citationLiu, Y. M., Liu, F., Iqbal, K., Grundke, I., & Gong, C. (2008) · FEBS Letters · doi:10.1016/j.febslet.2007.12.035 · Cited by 396 · see citing works
Self-citationSontag, E., Nunbhakdi‐Craig, V., Lee, G. S., Bloom, G. S., & Mumby, M. C. (1996) · Neuron · doi:10.1016/s0896-6273(00)80250-0 · Cited by 391 · see citing works
Mitochondrial Oxidative Stress Causes Hyperphosphorylation of Tau
Melov, S., Adlard, P. A., Morten, K., Johnson, F., Golden, T. R., Hinerfeld, D., Schilling, B., Mavros, C., Masters, C. L., Volitakis, I., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000536 · Cited by 363 · see citing works
The Microtubule-associated Protein Tau Is Extensively Modified with O-linked N-acetylglucosamine
Arnold, C. S., Johnson, G. W., Cole, R. N., Dong, D. L.-Y., Lee, M., & Hart, G. W. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.46.28741 · Cited by 361 · see citing works
MCI conversion to dementia and the APOE genotype
Mosconi, L., Perani, D., Sorbi, S., Herholz, K., Nacmias, B., Holthoff‐Detto, V., Salmon, É., Baron, J., Cristofaro, M. T. D., Padovani, A., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000147469.18313.3b · Cited by 344 · see citing works
Kuhl, D. E., Metter, E. J., Riege, W. H., & Phelps, M. E. (1982) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1982.15 · Cited by 338 · see citing works
Promotion of Hyperphosphorylation by Frontotemporal Dementia Tau Mutations
Alonso, A. D. C., Mederlyova, A., Novák, M., Grundke, I., & Iqbal, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405131200 · Cited by 330 · see citing works
Self-citationKhatoon, S., Grundke, I., & Iqbal, K. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09432.x · Cited by 304 · see citing works
Self-citationA Gene Expression Profile of Alzheimer's Disease
Loring, J. F., Wen, X., Lee, J. M., Seilhamer, J. J., & Somogyi, R. (2001) · DNA and Cell Biology · doi:10.1089/10445490152717541 · Cited by 300 · see citing works
Microtubule-Associated Protein Tau
Yen, S.-H. C., Nacharaju, P., Ko, L., Kenessey, Á., & Liu, W.-K. (1998) · Elsevier eBooks · doi:10.1016/b978-012734610-6/50012-9 · Cited by 284 · see citing works
PP2A mRNA Expression Is Quantitatively Decreased in Alzheimer's Disease Hippocampus
Vogelsberg-Ragaglia, V., Schuck, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7630 · Cited by 281 · see citing works
Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET.
Drzezga, A. E., Grimmer, T., Riemenschneider, M., Lautenschlager, N. T., Siebner, H. R., Alexopoulus, P., Minoshima, S., Schwaiger, M., & Kurz, A. (2005) · PubMed · Cited by 277 · see citing works
Planel, E., Miyasaka, T., Launey, T., Chui, D.-H., Tanemura, K., Sato, S., Murayama, O., Ishiguro, K., Tatebayashi, Y., & Takashima, A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5561-03.2004 · Cited by 261 · see citing works
The metabolic topography of normal aging
Moeller, J. R., Ishikawa, T., Dhawan, V., Spetsieris, P., Mandel, F., Alexander, G. E., Grady, C., Pietrini, P., & Eidelberg, D. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199605000-00005 · Cited by 254 · see citing works
Tau phosphorylation in Alzheimer's disease: pathogen or protector?
Lee, H., Perry, G. L., Moreira, P. I., Garrett, M. R., Liu, Q., Zhu, X., Takeda, A., Nunomura, A., & Smith, M. A. (2005) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2005.02.008 · Cited by 240 · see citing works
Tau-Mediated Cytotoxicity in a Pseudohyperphosphorylation Model of Alzheimer's Disease
Fath, T., Eidenmüller, J., & Brandt, R. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-22-09733.2002 · Cited by 233 · see citing works
Sontag, E., Luangpirom, A., Hladik, C., Mudrak, I., Ogris, E., Speciale, S., & White, C. L. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.4.287 · Cited by 228 · see citing works
Loessner, A., Alavi, A., Lewandrowski, K., Mozley, D. P., Souder, E., & Gur, R. E. (1995) · PubMed · Cited by 221 · see citing works
Planel, E., Yasutake, K., Fujita, S. C., & Ishiguro, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102780200 · Cited by 197 · see citing works
Pathways by Which Aβ Facilitates Tau Pathology
Blurton-Jones, M. M., & LaFerla, F. M. (2006) · Current Alzheimer Research · doi:10.2174/156720506779025242 · Cited by 195 · see citing works
Smith, G. S. (1992) · Archives of Neurology · doi:10.1001/archneur.1992.00530350056020 · Cited by 178 · see citing works
Goedert, M., Jakes, R., Qi, R. Z., Wang, J. H.-C., & Cohen, P. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65062804.x · Cited by 170 · see citing works
The selfish brain: competition for energy resources
Fehm, H. L., Kern, W., & Peters, A. (2006) · Progress in brain research · doi:10.1016/s0079-6123(06)53007-9 · Cited by 162 · see citing works
Alonso, A. D. C., Zaidi, T., Novák, M., Barra, H. S., Grundke, I., & Iqbal, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105365200 · Cited by 160 · see citing works
Self-citationPhosphorylated PP2A (tyrosine 307) is associated with Alzheimer neurofibrillary pathology
Liu, R., Zhou, X. ‐., Tanila, H., Bjorkdahl, C., Wang, J. ‐., Guan, Z. ‐., Cao, Y., Gustafsson, J. ‐., Winblad, B., & Pei, J. ‐. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2008.00249.x · Cited by 125 · see citing works
Mielke, R., Herholz, K., Grond, M., Kessler, J., & Heiß, W.-D. (1994) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000106692 · Cited by 121 · see citing works
Concurrent alterations of O‐GlcNAcylation and phosphorylation of tau in mouse brains during fasting
Li, X., Fen, L., Wang, J., & Gong, C. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04735.x · Cited by 116 · see citing works
Self-citationOxidative damage in Alzheimer's disease: the metabolic dimension
Perry, G. L., Nunomura, A., Hirai, K., Takeda, A., Aliev, G., & Smith, M. A. (2000) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(00)00006-x · Cited by 110 · see citing works
Liu, F., Zaidi, T., Iqbal, K., Grundke, I., & Gong, C. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00510-9 · Cited by 106 · see citing works
Self-citationFormation of aberrant phosphotau fibrillar polymers in neural cultured cells
Pérez, M., Hernández, F., Gómez‐Ramos, A., Smith, M. A., Perry, G. L., & Ávila, J. (2002) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2002.02794.x · Cited by 103 · see citing works
Tau hyperphosphorylation correlates with reduced methylation of protein phosphatase 2A
Zhou, X.-W., Gustafsson, J.-Α., Tanila, H., Björkdahl, C., Liu, R., Winblad, B. G., & Pei, J.-J. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.05.013 · Cited by 101 · see citing works
Physiological regulation of tau phosphorylation during hibernation
Su, B., Wang, X., Drew, K. L., Perry, G. L., Smith, M. A., & Zhu, X. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05294.x · Cited by 91 · see citing works
Metabolic/signal transduction hypothesis of Alzheimer?s disease and other tauopathies
Iqbal, K., & Grundke, I. (2005) · Acta Neuropathologica · doi:10.1007/s00401-004-0951-y · Cited by 91 · see citing works
Self-citationAbnormalities of Energy Metabolism in Alzheimer's Disease Studied with PETa
Heiss, W., Szelies, B., KESSLER, J., & Herholz, K. (1991) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1991.tb00192.x · Cited by 90 · see citing works
Deng, Y., Li, B., Liu, F., Iqbal, K., Grundke, I., Brandt, R., & Gong, C. (2007) · The FASEB Journal · doi:10.1096/fj.07-8309com · Cited by 80 · see citing works
Self-citationMcGeer, E. G., Peppard, R. P., McGeer, P. L., Tuokko, H., Crockett, D., Parks, R., Akiyama, H., Calne, D. B., Beattie, B. L., & Harrop, R. (1990) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100029930 · Cited by 76 · see citing works
A Metabolic Basis for Alzheimer Disease
Perry, G. L., Nunomura, A., Raina, A. K., Aliev, G. M., Siedlak, S. L., Harris, P. L. R., Casadesús, G., Petersen, R. B., Bligh-Glover, W. Z., Balraj, E. K., et al. (2003) · Neurochemical Research · doi:10.1023/a:1025678510480 · Cited by 55 · see citing works
Risk and protective factors for sporadic Alzheimer's disease.
Stožická, Z., Žilka, N., & Novák, M. (2007) · PubMed · Cited by 55 · see citing works
Mosconi, L., Tsui, W. H., Rusinek, H., et al. (2007) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-007-0406-5 · Cited by 51 · see citing works
Salmon, É., Maquet, P., Sadzot, B., et al. (1991) · PubMed · Cited by 50 · see citing works
Pei, J.-J., Sjögren, M., & Winblad, B. (2008) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e328314b78b · Cited by 49 · see citing works
Pietrini, P., Azari, N. P., Grady, C. L., Salerno, J. A., Gonzalez-Aviles, A., Heston, L. L., Pettigrew, K. D., Horwitz, B., Haxby, J. V., & Schapiro, M. B. (1993) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000107349 · Cited by 37 · see citing works
Cortical Glutaminase, β-Glucuronidase and Glucose Utilization in Alzheimer's Disease
McGeer, E. G., McGeer, P. L., Akiyama, H., & Harrop, R. (1989) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100029851 · Cited by 34 · see citing works
ANÇEVIĆ, V., ALAVI, A., Souder, E., Mozley, P. D., Gur, R. E., Bénard, F., & Munz, D. L. (2000) · Clinical Nuclear Medicine · doi:10.1097/00003072-200008000-00005 · Cited by 28 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- PLoS ONE 2007; 2: e536.
Cited by
Sorted by citations
Hart, G. W., Slawson, C., Ramirez-Correa, G., & Lagerlof, O. (2011) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060608-102511 · Cited by 1,317 · see citing works
Tau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113 · see citing works
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
Tau and neurodegenerative disease: the story so far
Iqbal, K., Liu, F., & Gong, C.-X. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.225 · Cited by 806 · see citing works
Self-citationIncreasing O-GlcNAc slows neurodegeneration and stabilizes tau against aggregation
Yuzwa, S. A., Shan, X., Macauley, M. S., Clark, T., Skorobogatko, Y., Vosseller, K., & Vocadlo, D. J. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.797 · Cited by 611 · see citing works
Morris, M., Knudsen, G. M., Maeda, S., Trinidad, J. C., Ioanoviciu, A., Burlingame, A. L., & Mucke, L. (2015) · Nature Neuroscience · doi:10.1038/nn.4067 · Cited by 472 · see citing works
The role of glucose transporters in brain disease: Diabetes and Alzheimer’s disease
Shah, K., DeSilva, S., & Abbruscato, T. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms131012629 · Cited by 288 · see citing works
The Emerging Link between O-GlcNAc and Alzheimer Disease
Zhu, Y., Shan, X., Yuzwa, S. A., & Vocadlo, D. J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r114.601351 · Cited by 267 · see citing works
Glucose Transporters in Brain: In Health and in Alzheimer’s Disease
Szablewski, L. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-160841 · Cited by 211 · see citing works
From Chronic Cerebral Hypoperfusion to Alzheimer-Like Brain Pathology and Neurodegeneration
Zhao, Y., & Gong, C.-X. (2015) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-014-0127-9 · Cited by 180 · see citing works
Self-citationReddy, P. H. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.06.012 · Cited by 147 · see citing works
A Mitocentric View of Alzheimer's Disease Suggests Multi-Faceted Treatments
Gibson, G. E., & Shi, Q. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-100336 · Cited by 124 · see citing works
Neuronal O-GlcNAcylation Improves Cognitive Function in the Aged Mouse Brain
Wheatley, E. G., Albarran, E., White, C. W., Bieri, G., Sanchez-Diaz, C., Pratt, K., Snethlage, C. E., Ding, J. B., & Villeda, S. A. (2019) · Current Biology · doi:10.1016/j.cub.2019.08.003 · Cited by 107 · see citing works
Targeting tau: clinical trials and novel therapeutic approaches
VandeVrede, L., Boxer, A. L., & Polydoro, M. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.134919 · Cited by 90 · see citing works
Cha, M.-Y., Cho, H. J., Kim, C., Jung, Y. O., Kang, M. J., Murray, M. E., Hong, H. S., Choi, Y.-J., Choi, H., Kim, D. K., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv358 · Cited by 95 · see citing works
Wang, L., Bharti, Kumar, R., Pavlov, P. F., & Winblad, B. (2021) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112915 · Cited by 92 · see citing works
O-GlcNAcase Inhibitor ASN90 is a Multimodal Drug Candidate for Tau and α-Synuclein Proteinopathies
Permanne, B., Sand, A., Ousson, S., Nény, M., Hantson, J., Schubert, R., Wiessner, C., Quattropani, A., & Beher, D. (2022) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00057 · Cited by 82 · see citing works
Gong, Y., & Lippa, C. F. (2010) · American Journal of Alzheimer's Disease & Other Dementias® · doi:10.1177/1533317510382893 · Cited by 76 · see citing works
Pinho, T. S., Correia, S. C., Perry, G., Ambrósio, A. F., & Moreira, P. I. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.10.037 · Cited by 70 · see citing works
(2020) · International Review of Neurobiology · doi:10.1016/bs.irn.2020.02.010 · Cited by 58 · see citing works
- Authors
- Liu, F., Shi, J., Tanimukai, H., Gu, J., Gu, J., Grundke-Iqbal, I., Iqbal, K., & Gong, C.-X.
- Affiliations
- Nantong University (CN)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-05-18
- Volume
- 132
- Issue
- 7
- Pages
- 1820-1832
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC2702834
- OpenAlex
- W2171758504
- Cited by
- 439
- References
- 69
- Citations by year
- 2026: 21 · 2025: 27 · 2024: 41 · 2023: 31 · 2022: 30 · 2021: 33 · 2020: 36 · 2019: 23 · 2018: 29 · 2017: 29 · 2016: 21 · 2015: 15 · 2014: 33 · 2013: 15 · 2012: 14
- FWCI
- 11.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P30-AG-19610, R01AG019158, R01AG027429, P30AG019610)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, O-GlcNAcylation, tau hyperphosphorylation, brain glucose metabolism, protein phosphatase 2A, hexosamine biosynthetic pathway, neurofibrillary degeneration, O-GlcNAc transferase, post-translational modification, fasting
- MeSH terms
- Aged, 80 and over, Alzheimer Disease, Brain, Cells, Cultured, Female, Glucose, Hexosamines, Humans, Male, Phosphorylation, Down-Regulation, tau Proteins, N-Acetylglucosaminyltransferases, Protein Phosphatase 2
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.
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