Amyloid-beta peptide decreases expression and function of glutamate transporters in nervous system cells
Abstract
Glutamate is an essential excitatory neurotransmitter that regulates brain functions, and its activity is tightly regulated by glutamate transporters. Excess glutamate in the synaptic cleft and dysfunction of excitatory amino acid transporters have been shown to be involved in development of Alzheimer's disease, but the precise regulatory mechanism is poorly understood. Using a D-[ 3 H]-aspartic acid uptake assay, we found that Aβ 1-42 oligomers impaired glutamate uptake in astrocytes and neurons. In astrocytes, this process was accompanied by reduced expression of GLT-1 and GLAST as detected by Western blot and immunocytofluorescence. However, mRNA levels of EAATs detected by qPCR in astrocytes and neurons were not altered, which suggests that this process is post-translational. Co-localization analysis using immunocytofluorescence showed that ubiquitylation of GLT-1 significantly increased. Therefore, we hypothesized that Aβ 1-42 oligomers-induced endocytosis of astrocytic GLT-1 may be involved in ubiquitylation. In addition, Aβ 1-42 oligomers enhanced secretion of IL-1β, TNF-α, and IL-6 into culture supernatant, which may be correlated with an inflammatory response and altered EAATs expression or function in Alzheimer's disease. These findings support the idea that dysregulation of the glutamatergic system may play a significant role in pathogenesis of Alzheimer's disease. Furthermore, enhancing expression or function of EAATs in astrocytes and neurons might be a new thera…
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Typically, activated microglia displays ameboid morphologies and induces astrocytic activation.
“Typically, activated microglia displays ameboid morphologies [112] and induces astrocytic activation [106, 113, 114].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [113]
Aβ and inflammation decrease GLAST expression and function, weaken glutamate clearance, and favor excitotoxicity.
“prior reports have shown that Aβ [113] and inflammation [96] decrease GLAST expression and function [114], weaken glutamate clearance [115, 116], and favor excitotoxicity [25, 28].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [113]
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · see citing works
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · see citing works
Danbolt, N. C. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00067-8 · Cited by 4,068 · see citing works
NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.-C., et al. (2013) · Nature · doi:10.1038/nature11729 · Cited by 2,898 · see citing works
The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes
Benilova, I., Karran, E., & De Strooper, B. (2012) · Nature Neuroscience · doi:10.1038/nn.3028 · Cited by 1,962 · see citing works
Epilepsy and Exacerbation of Brain Injury in Mice Lacking the Glutamate Transporter GLT-1
Tanaka, K., Watase, K., Manabe, T., Yamada, K., Watanabe, M., Takahashi, K., Iwama, H., Nishikawa, T., Ichihara, N., Kikuchi, T., et al. (1997) · Science · doi:10.1126/science.276.5319.1699 · Cited by 1,755 · see citing works
Amyloid-β–induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks
Palop, J. J., & Mucke, L. (2010) · Nature Neuroscience · doi:10.1038/nn.2583 · Cited by 1,651 · see citing works
A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity
Weggen, S., Eriksen, J. L., Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter, T., et al. (2001) · Nature · doi:10.1038/35102591 · Cited by 1,388 · see citing works
Amyloid β-protein (Aβ) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways
Bitan, G., Kirkitadze, M. D., Lomakin, A., Vollers, S. S., Benedek, G. B., & Teplow, D. B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222681699 · Cited by 1,280 · see citing works
Astrocyte glutamate transport: Review of properties, regulation, and physiological functions
Anderson, C. M., & Swanson, R. A. (2000) · Glia · doi:10.1002/1098-1136(200010)32:1 · Cited by 1,218 · see citing works
Nonsteroidal Antiinflammatory Drugs and the Risk of Alzheimer's Disease
in 't Veld, B. A., Ruitenberg, A., Hofman, A., Launer, L. J., van Duijn, C. M., Stijnen, T., Breteler, M. M. B., & Stricker, B. H. C. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa010178 · Cited by 1,196 · see citing works
Lacor, P. N., Buniel, M. C., Furlow, P. W., Sanz Clemente, A., Velasco, P. T., Wood, M., Viola, K. L., & Klein, W. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3501-06.2007 · Cited by 1,188 · see citing works
Systemic inflammation and disease progression in Alzheimer disease
Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., & Perry, V. H. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b6bb95 · Cited by 1,139 · see citing works
Li, S., Hong, S., Shepardson, N. E., Walsh, D. M., Shankar, G. M., & Selkoe, D. (2009) · Neuron · doi:10.1016/j.neuron.2009.05.012 · Cited by 972 · see citing works
Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer?s disease
HYND, M. (2004) · Neurochemistry International · doi:10.1016/j.neuint.2004.03.007 · Cited by 938 · see citing works
Innate immunity in Alzheimer's disease
Heneka, M. T., Golenbock, D. T., & Latz, E. (2015) · Nature Immunology · doi:10.1038/ni.3102 · Cited by 902 · see citing works
Appraising the brain's energy budget
Raichle, M. E., & Gusnard, D. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172399499 · Cited by 888 · see citing works
Jin, M., Shepardson, N., Yang, T., Chen, G., Walsh, D., & Selkoe, D. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017033108 · Cited by 876 · see citing works
Koffie, R. M., Meyer-Luehmann, M., Hashimoto, T., Adams, K. W., Mielke, M. L., Garcia-Alloza, M., Micheva, K. D., Smith, S. J., Kim, M. L., Lee, V. M., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811698106 · Cited by 850 · see citing works
Lehre, K. P., & Danbolt, N. C. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-21-08751.1998 · Cited by 675 · see citing works
Li, S., Jin, M., Koeglsperger, T., Shepardson, N. E., Shankar, G. M., & Selkoe, D. J. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0203-11.2011 · Cited by 664 · see citing works
Aβ toxicity in Alzheimer’s disease: globular oligomers (ADDLs) as new vaccine and drug targets
Klein, W. L. (2002) · Neurochemistry International · doi:10.1016/s0197-0186(02)00050-5 · Cited by 541 · see citing works
Kuperstein, I., Broersen, K., Benilova, I., Rozenski, J., Jonckheere, W., Debulpaep, M., Vandersteen, A., Segers‐Nolten, I., Van Der Werf, K., Subramaniam, V., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.211 · Cited by 532 · see citing works
Brain Glutamate Transporter Proteins Form Homomultimers
Haugeto, Ø., Ullensvang, K., Levy, L. M., Chaudhry, F. A., Honoré, T., Nielsen, M., Lehre, K. P., & Danbolt, N. C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27715 · Cited by 489 · see citing works
Klein, W. L., Stine, W. B., & Teplow, D. B. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.02.010 · Cited by 487 · see citing works
Lauderback, C. M., Hackett, J. M., Huang, F. F., Keller, J. N., Szweda, L. I., Markesbery, W. R., & Butterfield, D. A. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00451.x · Cited by 464 · see citing works
Neuronal and glial calcium signaling in Alzheimer’s disease
Mattson, M. P., & Chan, S. L. (2003) · Cell Calcium · doi:10.1016/s0143-4160(03)00128-3 · Cited by 454 · see citing works
Molecular Mechanisms of Amyloid Oligomers Toxicity
Kayed, R., & Lasagna‐Reeves, C. A. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129001 · Cited by 417 · see citing works
Sastre, M., Dewachter, I., Landreth, G. E., Willson, T. M., Klockgether, T., LEUVEN, F. V., & Heneka, M. T. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-30-09796.2003 · Cited by 359 · see citing works
LI, S., MALLORY, M., ALFORD, M., TANAKA, S., & MASLIAH, E. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199708000-00008 · Cited by 343 · see citing works
Abdul, H. M., Sama, M. A., Furman, J. L., Mathis, D. M., Beckett, T. L., Weidner, A. M., Patel, E., Baig, I., Murphy, M. P., LeVine, H., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.1064-09.2009 · Cited by 319 · see citing works
Jacob, C. P., Koutsilieri, E., Bartl, J., Neuen-Jacob, E., Arzberger, T., Zander, N., Ravid, R., Roggendorf, W., Riederer, P., & Grünblatt, E. (2007) · Journal of Alzheimer's Disease · doi:10.3233/jad-2007-11113 · Cited by 317 · see citing works
Lipids revert inert Aβ amyloid fibrils to neurotoxic protofibrils that affect learning in mice
Martins, I. C., Kuperstein, I., Wilkinson, H. R., Maes, E., Vanbrabant, M., Jonckheere, W., Gelder, P. V., Hartmann, D., D’Hooge, R., Strooper, B. D., et al. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601953 · Cited by 311 · see citing works
Regulation of the glial Na+-dependent glutamate transporters by cyclic AMP analogs and neurons.
Schlag, B. D., Vondrasek, J. R., Munir, M., Kalandadze, A., Zelenaia, O. A., Rothstein, J. D., & Robinson, M. B. (1998) · Molecular Pharmacology · doi:10.1124/mol.53.3.355 · Cited by 303 · see citing works
Petr, G. T., Sun, Y., Frederick, N. M., Zhou, Y., Dhamne, S. C., Hameed, M. Q., Miranda, C., Bedoya, E. A., Fischer, K. D., Armsen, W., et al. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.4255-14.2015 · Cited by 297 · see citing works
Aβ42 is More Rigid than Aβ40 at the C Terminus: Implications for Aβ Aggregation and Toxicity
Yan, Y., & Wang, C. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.09.046 · Cited by 271 · see citing works
Chen, W., Mahadomrongkul, V., Berger, U. V., Bassan, M., DeSilva, T. M., Tanaka, K., Irwin, N., Aoki, C. J., & Rosenberg, P. A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1586-03.2004 · Cited by 267 · see citing works
Furness, D. N., Dehnes, Y., Akhtar, A. Q., Rossi, D. J., Hamann, M., Grutle, N. J., Gundersen, V., Holmseth, S., Lehre, K. P., Ullensvang, K., et al. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.08.043 · Cited by 254 · see citing works
Surface diffusion of astrocytic glutamate transporters shapes synaptic transmission
Murphy-Royal, C., Dupuis, J. P., Varela, J. A., Panatier, A., Pinson, B., Baufreton, J., Groc, L., & Oliet, S. H. R. (2015) · Nature Neuroscience · doi:10.1038/nn.3901 · Cited by 252 · see citing works
Gegelashvili, G., Danbolt, N. C., & Schousboe, A. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69062612.x · Cited by 238 · see citing works
Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1
Yang, Y., Gozen, O., Watkins, A., Lorenzini, I., Lepore, A., Gao, Y., Vidensky, S., Brennan, J., Poulsen, D., Won Park, J., et al. (2009) · Neuron · doi:10.1016/j.neuron.2009.02.010 · Cited by 237 · see citing works
Positive and negative regulation of EAAT2 by NF‐κB: a role for N‐myc in TNFα‐controlled repression
Sitcheran, R., Gupta, P., Fisher, P., & Baldwin, A. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600555 · Cited by 226 · see citing works
Matos, M., Augusto, E., Oliveira, C. R., & Agostinho, P. M. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.08.022 · Cited by 223 · see citing works
Chen, W., Aoki, C. J., Mahadomrongkul, V., Gruber, C. E., Wang, G. J., Blitzblau, R. C., Irwin, N., & Rosenberg, P. A. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-06-02142.2002 · Cited by 208 · see citing works
Ullensvang, K., Lehre, K. P., Storm‐Mathisen, J., & Danbolt, N. C. (1997) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1997.tb01522.x · Cited by 199 · see citing works
Scimemi, A., Meabon, J. S., Woltjer, R. L., Sullivan, J. M., Diamond, J. S., & Cook, D. G. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.5274-12.2013 · Cited by 185 · see citing works
Liu, Z., Li, Z., Liu, L., Tang, W., Wang, Y., Dong, M., & Xiao, C. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00261 · Cited by 153 · see citing works
Zumkehr, J., Rodríguez‐Ortiz, C. J., Cheng, D., Kieu, Z., Wai, T., Hawkins, C., Kilian, J., Lim, S., Medeiros, R., & Kitazawa, M. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.04.005 · Cited by 152 · see citing works
Abnormal Glutamate Transport Function in Mutant Amyloid Precursor Protein Transgenic Mice
Masliah, E., Alford, M. F., Mallory, M. E., Rockenstein, E. M., Moechars, D., & LEUVEN, F. V. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7386 · Cited by 145 · see citing works
Scott, H. L., Pow, D. V., Tannenberg, A. E. G., & Dodd, P. R. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-03-j0004.2002 · Cited by 127 · see citing works
Weng, H., Chen, J.-H., & Cata, J. P. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2005.11.061 · Cited by 111 · see citing works
On the potential role of glutamate transport in mental fatigue.
Rönnbäck, L., & Hansson, E. (2004) · Journal of Neuroinflammation · doi:10.1186/1742-2094-1-22 · Cited by 105 · see citing works
Liu, L., & Chan, C. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.08.016 · Cited by 104 · see citing works
Yan, X., Yadav, R., Gao, M., & Weng, H. (2014) · Glia · doi:10.1002/glia.22665 · Cited by 93 · see citing works
García‐Tardón, N., González‐González, I. M., de Villarreal, J. M., Fernández-Sánchez, E., Giménez, C., & Zafra, F. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.355909 · Cited by 89 · see citing works
Substrate-induced up-regulation of Na+-dependent glutamate transport activity
Munir, M. (2000) · Neurochemistry International · doi:10.1016/s0197-0186(00)00018-8 · Cited by 89 · see citing works
Mechanism of raloxifene-induced upregulation of glutamate transporters in rat primary astrocytes
Karki, P., Webb, A., Zerguine, A. M., Choi, J., Son, D., & Lee, E.-S. (2014) · Glia · doi:10.1002/glia.22679 · Cited by 84 · see citing works
Aberrant Detergent-Insoluble Excitatory Amino Acid Transporter 2 Accumulates in Alzheimer Disease
Woltjer, R. L., Duerson, K. C., Fullmer, J. M., Mookherjee, P., Ryan, A. M., Montine, T. J., Kaye, J. A., Quinn, J. F., Silbert, L. C., Erten‐Lyons, D., et al. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181e24adb · Cited by 73 · see citing works
Sheldon, A. L., González, M. I., Krizman, E. N., Susarla, B. T. S., & Robinson, M. B. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2008.07.010 · Cited by 69 · see citing works
Awabdh, S. A., Gupta, S., Sheehan, D. F., Muir, J., Norkett, R., Twelvetrees, A. E., Griffin, L. D., & Kittler, J. T. (2016) · Glia · doi:10.1002/glia.22997 · Cited by 68 · see citing works
González‐González, I. M., García‐Tardón, N., Giménez, C., & Zafra, F. (2008) · Glia · doi:10.1002/glia.20670 · Cited by 67 · see citing works
Current thinking on the mechanistic basis of Alzheimer's and implications for drug development
Ising, C., Stanley, M., & Holtzman, D. (2015) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.200 · Cited by 59 · see citing works
de Villarreal, J. M., García‐Tardón, N., Ibáñez, I., Giménez, C., & Zafra, F. (2012) · Glia · doi:10.1002/glia.22354 · Cited by 53 · see citing works
Excitatory Amino Acid Transporter EAAT‐2 in Tangle‐bearing Neurons in Alzheimer's Disease
Thal, D. R. (2002) · Brain Pathology · doi:10.1111/j.1750-3639.2002.tb00457.x · Cited by 49 · see citing works
Differential involvement of TNFα in hypoxic suppression of astrocyte glutamate transporters
Boycott, H. E., Wilkinson, J. A., Boyle, J. P., Pearson, H. A., & Peers, C. (2008) · Glia · doi:10.1002/glia.20673 · Cited by 43 · see citing works
Ceftriaxone Protects Astrocytes from MPP+ via Suppression of NF-ΚB/JNK/c-Jun Signaling
Zhang, Y., Zhang, X., & Qu, S. (2015) · Molecular Neurobiology · doi:10.1007/s12035-014-8845-z · Cited by 39 · see citing works
Self-citationHan, X., Yang, L., Du, H., Sun, Q., Wang, X., Cong, L., Liu, X., Yin, L., Li, S., & Du, Y. (2015) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-015-0268-5 · Cited by 35 · see citing works
Abe, K., & Misawa, M. (2002) · Neuroscience Research · doi:10.1016/s0168-0102(02)00190-6 · Cited by 31 · see citing works
Alterations of some membranetransportproteins in Alzheimer's disease: role of amyloid β-peptide
Rukhsana Sultana, A., & Butterfield, D. A. (2007) · Molecular BioSystems · doi:10.1039/b715278g · Cited by 28 · see citing works
Aβ42 oligomers modulate β-secretase through an XBP-1s-dependent pathway involving HRD1
Gerakis, Y., Dunys, J., Bauer, C., & Checler, F. (2016) · Scientific Reports · doi:10.1038/srep37436 · Cited by 25 · see citing works
Rong, X., Tan, F., Wu, X., Zhang, X., Lu, L., Zou, X., & Qu, S. (2016) · Scientific Reports · doi:10.1038/srep34522 · Cited by 16 · see citing works
Self-citationZhang, X., Yao, N., & Chergui, K. (2016) · Learning & Memory · doi:10.1101/lm.043190.116 · Cited by 10 · see citing works
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Flagged first, then by citations
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Sorted by citations
Li, S., & Selkoe, D. J. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15007 · Cited by 264 · see citing works
Reactive astrogliosis: A friend or foe in the pathogenesis of Alzheimer’s disease
Kumar, A., Fontana, I. C., & Nordberg, A. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15565 · Cited by 150 · see citing works
Role of Aβ in Alzheimer’s-related synaptic dysfunction
Zhang, H., Jiang, X., Ma, L., Wei, W., Li, Z., Chang, S., Wen, J., Sun, J., & Li, H. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.964075 · Cited by 144 · see citing works
Amyloid-β oligomers in cellular models of Alzheimer’s disease
Fontana, I. C., Zimmer, A. R., Rocha, A. S., Gosmann, G., Souza, D. O., Lourenco, M. V., Ferreira, S. T., & Zimmer, E. R. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15030 · Cited by 115 · see citing works
Tong, H., Zhang, X., Meng, X., Lu, L., Mai, D., & Qu, S. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00165 · Cited by 109 · see citing works
Self-citationAstrocyte and glutamate involvement in the pathogenesis of epilepsy in Alzheimer's disease
Dejakaisaya, H., Kwan, P., & Jones, N. C. (2021) · Epilepsia · doi:10.1111/epi.16918 · Cited by 62 · see citing works
Role of Neuron and Glia in Alzheimer’s Disease and Associated Vascular Dysfunction
Bandyopadhyay, S. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.653334 · Cited by 62 · see citing works
Wei, Z., Meng, X., Fatimy, R. E., Sun, B., Mai, D., Zhang, J., Arora, R., Zeng, A., Xu, P., Qu, S., et al. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104617 · Cited by 55 · see citing works
Self-citationDahlmanns, M., Dahlmanns, J. K., Savaskan, N. E., Steiner, H. H., & Yakubov, E. (2023) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2803057 · Cited by 52 · see citing works
Astrocytic glutamatergic transporters are involved in Aβ-induced synaptic dysfunction
Huang, S., Tong, H., Lei, M., Zhou, M., Guo, W., Li, G., Tang, X., Li, Z., Mo, M., Zhang, X., et al. (2017) · Brain Research · doi:10.1016/j.brainres.2017.10.011 · Cited by 52 · see citing works
Self-citationNoradrenaline in the aging brain: Promoting cognitive reserve or accelerating Alzheimer's disease?
Mather, M. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.05.013 · Cited by 53 · see citing works
Zhang, Y., Meng, X., Jiao, Z., Liu, Y., Zhang, X., & Qu, S. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00609 · Cited by 49 · see citing works
Self-citationLong, J.-Y., Chen, J., Liao, Y., Zhou, Y., Liang, B., & Zhou, Y. (2020) · Behavioral and Brain Functions · doi:10.1186/s12993-020-00166-6 · Cited by 40 · see citing works
Fontana, I. C., de Souza, D. G., Souza, D. O., Gee, A. D., Zimmer, E. R., & Bongarzone, S. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01572 · Cited by 34 · see citing works
Zoltowska, K. M., Maesako, M., Meier, J. C., & Berezovska, O. (2018) · Scientific Reports · doi:10.1038/s41598-018-26888-2 · Cited by 27 · see citing works
McCarty, M. F., DiNicolantonio, J. J., & Lerner, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042140 · Cited by 26 · see citing works
Xu, H., Jiang, H. F., & Xie, J. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00071 · Cited by 24 · see citing works
Mosalam, E. M., Abdel‐Bar, H. M., Elberri, A. I., Abdallah, M. S., Zidan, A. A., Batakoushy, H. A., & Mansour, H. E. A. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.133742 · Cited by 23 · see citing works
Liu, M., Zhu, J., Zheng, J., Han, X., Jiang, L., Tong, X., Ke, Y., Guo, Z., Huang, W., Cong, J., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115343 · Cited by 22 · see citing works
Self-citationGao, J., Liu, L., Liu, C., Fan, S., Liu, L., Liu, S., Xian, X., & Li, W. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.580772 · Cited by 21 · see citing works
Regional brain iron correlates with transcriptional and cellular signatures in Alzheimer's disease
Yang, A., Luan, J., Xu, M., Du, L., Lv, K., Hu, P., Shu, N., Yuan, Z., Shmuel, A., & Ma, G. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14459 · Cited by 14 · see citing works
de Mello, L. R., Hamley, I. W., Miranda, A., Alves, W. A., & da Silva, E. R. (2019) · Journal of Peptide Science · doi:10.1002/psc.3170 · Cited by 14 · see citing works
Li, L., Li, W., Jiang, W., & Xu, R. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-01827-5 · Cited by 13 · see citing works
Henao‐Restrepo, J., López‐Murillo, C., Valderrama‐Carmona, P., Orozco‐Santa, N., Gomez, J., Gutiérrez‐Vargas, J., Moraga, R., Toledo, J., Littau, J. L., Härtel, S., et al. (2023) · Brain Pathology · doi:10.1111/bpa.13119 · Cited by 11 · see citing works
A nonlinear meccano for Alzheimer's emergence by amyloid β-mediated glutamatergic hyperactivity
Bonifazi, G., Luchena, C., Gaminde‐Blasco, A., Ortiz-Sanz, C., Capetillo‐Zarate, E., Matute, C., Alberdi, E. M., & Pittà, M. D. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106473 · Cited by 9 · see citing works
Li, S., Wang, J., Guo, Q., Bai, Y., Liu, W., Hodgetts, K. J., Rosenberg, P. A., & Selkoe, D. J. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-00882 · Cited by 6 · see citing works
Liu, F.-W., Liu, Y., Shen, X.-R., Du, J., Zhang, H., & Hou, X. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1391082 · Cited by 5 · see citing works
Sułkowski, G., Wencel, P. L., Dąbrowska‐Bouta, B., Strużyńska, L., & Strosznajder, R. P. (2022) · Folia Neuropathologica · doi:10.5114/fn.2022.114302 · Cited by 4 · see citing works
Sardari, M., Sahafi, O. H., & Rezayof, A. (2025) · Brain Research · doi:10.1016/j.brainres.2025.150040 · Cited by 3 · see citing works
Alzheimer's Disease Biomarker-Nigeria (ADIBIO-N): Cohort description and baseline data report
Ucheagwu, V. A., Morgan, D., Rose, S., Odilora, C., Okafor, C., & Giordani, B. J. (2025) · Journal of Alzheimer's Disease · doi:10.1177/13872877251394384 · Cited by 2 · see citing works
Modeling of neuronal hyperexcitability modulated by Aβ-mediated astrocyte dysfunction
Li, Y., Yang, X., Yang, H., & Kurths, J. (2025) · Physical review. E · doi:10.1103/1r82-x54p · Cited by 2 · see citing works
Zhao, P., Fadel, O. E., Le, A., Mangleburg, C. G., Dhindsa, J. S., Wu, T., Zhao, J., Huang, M., Amoh, B. K., Marella, A. S., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03479-6 · Cited by 1 · see citing works
Is amyloid beta peptide a driver of inflammaging?
Kechko, O. I., Moskalev, A. A., Franceschi, C., Mitkevich, V. A., & Makarov, A. А. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103280 · Cited by 1 · see citing works
Liu, F.-W., Zhang, X.-R., Cong, Y.-F., Liu, Y., Zhang, H., & Hou, X. (2025) · Reviews in the Neurosciences · doi:10.1515/revneuro-2024-0143 · Cited by 1 · see citing works
Self-citationSerrano, S. (2006) · Cuadernos hispanoamericanos
The nonlinear meccano of hyperactivity in AlzheimerPreprint
Bonifazi, G., Luchena, C., Gaminde-Blasco, A., Ortiz-Sanz, C., Capetillo-Zárate, E., Matute, C., Alberdi, E., & Pittà, M. D. (2023) · bioRxiv · doi:10.1101/2023.10.09.561541
Glial Cell Biology and Their Multifaceted Functions in Alzheimer's Disease
Laadraoui, J., Kabdy, H., Azraida, H., Aimrane, A., & Smimih, K. (2023) · Advances in bioinformatics and biomedical engineering book series · doi:10.4018/978-1-6684-9675-6.ch015
Systems genetic dissection of Alzheimer’s disease brain gene expression networksPreprint
Zhao, P., Fadel, O. E., Le, A., Mangleburg, C. G., Dhindsa, J. S., Wu, T., Zhao, J., Huang, M., Amoh, B. K., Marella, A. S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.04.616661
Wang, W., Wu, S., Zhang, L., Li, Y., Tong, L., Duan, A., Lv, S., Chen, X., & Li, B. (2025) · Toxicology · doi:10.1016/j.tox.2025.154273
Li, Y., & Yang, X. (2026) · Nonlinear Dynamics · doi:10.1007/s11071-026-12358-2
Glutamine metabolism in health and disease
Zhao, J., Lin, Y., Gao, R., Gao, H., & Li, L. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02981-1
- Authors
- Tong, H., Zhang, X., Meng, X., Xu, P., Zou, X., & Qu, S.
- Affiliations
- The First People's Hospital of Shunde (CN)
- Southern Medical University (CN)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Corresponding author
- Xu, Pingyi
- Zou, Xiaoming
- Qu, Shaogang
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 85
- Pages
- 75-84
- ISSN
- 1357-2725 (ISSN-L)
- OpenAlex
- W2587701879
- Cited by
- 42
- References
- 73
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 2
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31570716, U1603281)
- Science and Technology Planning Project of Guangdong Province (2012B050200003, 2013B021800305, 2016A050502025)
- Science and Technology Planning Project of Guangzhou (2013J4500018, 2014J4100008)
- Scientific and Technological Innovation Programs of the Higher Education Institution in Guangdong (2013KJCX0041)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- glutamate transporters, GLT-1, GLAST, astrocytes, neurons, glutamate uptake, ubiquitination, endocytosis, neuroinflammation, inflammatory cytokines, Alzheimer's disease, glutamatergic system
- MeSH terms
- Animals, Astrocytes, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Blotting, Western, Down-Regulation, Amyloid beta-Peptides, Vesicular Glutamate Transport Proteins, Mice
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