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Distinct Signaling Pathways Regulate TREM2 Phagocytic and NFκB Antagonistic Activities
Open accessAbstract
Several genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) have been shown to increase the risk of developing Alzheimer's disease (AD) supporting a role of microglia and immune cells in the pathobiology of AD. We have employed an ectopic model of TREM2 and DAP12 expression in HEK293 cells to study selectively TREM2 dependent signaling and phagocytic functions and evaluated the effects of some of the TREM2 mutations associated with AD. We show that shedding of the TREM2 N-terminal domain does not affect the inhibition of NFκB activation induced by TREM2 while it completely blocks phagocytosis suggesting that TREM2 anti-inflammatory properties can be mediated by the TREM2 C-terminal fragment while the phagocytic activity requires the full-length receptor. In addition, we confirm in that model that apolipoprotein E (APOE) is a ligand for TREM2 and triggers TREM2 signaling. In particular, we show that APOE4 stimulates spleen tyrosine kinase (SYK) activation more potently than APOE2 in a TREM2 dependent manner. Interestingly, TREM2 appears to antagonize NFκB activation induced by phorbol ester but is unable to prevent TNFα induction of NFκB activation suggesting that TREM2 antagonizes inflammatory events triggered downstream of PKC. TREM2 mutations drastically impact TREM2 phagocytosis as well as its ability to antagonize NFκB activation and notably prevent the activation of the PI3K/AKT pathway observed with wild-type TREM2. Overall our data suggest that TREM2 dependent phagocytosis requires an activation of the SYK/PI3K/AKT/PLCγ pathways while the suppression of NFκB activation by TREM2 is independent of SYK, PI3K, and PLCγ activities. This model of ectopic TREM2-DAP12 co-expression appears suitable to study TREM2 signaling as several biological functions of TREM2 and TREM2 mutations that have been previously described in myeloid and microglial cells were also replicated in this model.
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“In addition, SYK has been identified as the central kinase that instructs signaling and effector functions downstream of TREM2, CD33, and CD22 receptors (Clark and Giltiay, 2018; Wissfeld et al., 2021; Yao et al., 2019).”
From SYK coordinates neuroprotective microglial responses in neurodegenerative disease (2022) · cites this paper as Yao et al., 2019
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“Though previous in vitro studies have shown that TREM2 activation can provoke SYK signaling (Yao et al., 2019)”
From SYK coordinates neuroprotective microglial responses in neurodegenerative disease (2022) · cites this paper as Yao et al., 2019
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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
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
TREM2 Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020
Variant of TREM2 Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208
The Cellular Phase of Alzheimer’s Disease
De Strooper, B., & Karran, E. (2016) · Cell · doi:10.1016/j.cell.2015.12.056 · Cited by 1,990
TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model
Wang, Y., Cella, M., Mallinson, K., Ulrich, J. D., Young, K. L., Robinette, M. L., Gilfillan, S., Krishnan, G. M., Sudhakar, S., Zinselmeyer, B. H., et al. (2015) · Cell · doi:10.1016/j.cell.2015.01.049 · Cited by 1,736
The microglial sensome revealed by direct RNA sequencing
Hickman, S. E., Kingery, N. D., Ohsumi, T. K., Borowsky, M. L., Wang, L.-C., Means, T. K., & El Khoury, J. (2013) · Nature Neuroscience · doi:10.1038/nn.3554 · Cited by 1,511
The SYK tyrosine kinase: A crucial player in diverse biological functions
Mócsai, A., Ruland, J., & Tybulewicz, V. L. J. (2010) · Nature Reviews Immunology · doi:10.1038/nri2765 · Cited by 1,368
Takahashi, K., Rochford, C. D. P., & Neumann, H. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041611 · Cited by 1,124
Yeh, F. L., Wang, Y., Tom, I., Gonzalez, L. C., & Sheng, M. (2016) · Neuron · doi:10.1016/j.neuron.2016.06.015 · Cited by 943
Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells
Lanier, L. L., Corliss, B. C., Wu, J., Leong, C. C., & Phillips, J. H. (1998) · Nature · doi:10.1038/35642 · Cited by 907
TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques
Wang, Y., Ulland, T. K., Ulrich, J. D., Song, W., Tzaferis, J. A., Hole, J. T., Yuan, P., Mahan, T. E., Shi, Y., Gilfillan, S., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20151948 · Cited by 840
Yuan, P., Condello, C., Keene, C. D., Wang, Y., Bird, T. D., Paul, S. M., Luo, W., Colonna, M., Baddeley, D., & Grutzendler, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.003 · Cited by 817
TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis
Kleinberger, G., Yamanishi, Y., Suárez-Calvet, M., Czirr, E., Lohmann, E., Cuyvers, E., Struyfs, H., Pettkus, N., Wenninger-Weinzierl, A., Mazaheri, F., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009093 · Cited by 798
TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function
Zhao, Y., Wu, X., Li, X., Jiang, L.-L., Gui, X., Liu, Y., Sun, Y., Zhu, B., Piña-Crespo, J. C., Zhang, M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.01.031 · Cited by 763
Combs, C. K., Karlo, J. C., Kao, S.-C., & Landreth, G. E. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-04-01179.2001 · Cited by 721
TREMs in the immune system and beyond
Colonna, M. (2003) · Nature Reviews Immunology · doi:10.1038/nri1106 · Cited by 701
Cutting Edge: TREM-2 Attenuates Macrophage Activation
Turnbull, I. R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., & Colonna, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.6.3520 · Cited by 688
Jay, T. R., Miller, C. M., Cheng, P. J., Graham, L. C., Bemiller, S., Broihier, M. L., Xu, G., Margevicius, D., Karlo, J. C., Sousa, G. L., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20142322 · Cited by 682
Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)
Atagi, Y., Liu, C.-C., Painter, M. M., Chen, X.-F., Verbeeck, C., Zheng, H., Li, X., Rademakers, R., Kang, S. S., Xu, H., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.679043 · Cited by 587
Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE
Parhizkar, S., Arzberger, T., Brendel, M., Kleinberger, G., Deussing, M., Focke, C., Nuscher, B., Xiong, M., Ghasemigharagoz, A., Katzmarski, N., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0296-9 · Cited by 555
TREM2 sustains microglial expansion during aging and response to demyelination
Poliani, P. L., Wang, Y., Fontana, E., Robinette, M. L., Yamanishi, Y., Gilfillan, S., & Colonna, M. (2015) · Journal of Clinical Investigation · doi:10.1172/jci77983 · Cited by 525
Leyns, C. E. G., Ulrich, J. D., Finn, M. B., Stewart, F. R., Koscal, L. J., Remolina Serrano, J., Robinson, G. O., Anderson, E., Colonna, M., & Holtzman, D. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710311114 · Cited by 517 · cited 1×
“, 2017) or on the opposite prevents the neurodegeneration induced by the tauopathy (Leyns et al., 2017).”
BackgroundBouchon, A., Hernández-Munain, C., Cella, M., & Colonna, M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.8.1111 · Cited by 460
Disease Progression-Dependent Effects of TREM2 Deficiency in a Mouse Model of Alzheimer's Disease
Jay, T. R., Hirsch, A. M., Broihier, M. L., Miller, C. M., Neilson, L. E., Ransohoff, R. M., Lamb, B. T., & Landreth, G. E. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2110-16.2016 · Cited by 457
Hamerman, J. A., Jarjoura, J. R., Humphrey, M. B., Nakamura, M. C., Seaman, W. E., & Lanier, L. L. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.4.2051 · Cited by 440
TREM2, microglia, and neurodegenerative diseases
Yeh, F. L., Hansen, D. V., & Sheng, M. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.008 · Cited by 440
TREM2 variants: new keys to decipher Alzheimer disease pathogenesis
Colonna, M., & Wang, Y. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.7 · Cited by 418
TREM2- and DAP12-dependent activation of PI3K requires DAP10 and is inhibited by SHIP1
Peng, Q., Malhotra, S., Torchia, J. A., Kerr, W. G., Coggeshall, K. M., & Humphrey, M. B. (2010) · Science Signaling · doi:10.1126/scisignal.2000500 · Cited by 413
Soluble TREM2 induces inflammatory responses and enhances microglial survival
Zhong, L., Chen, X., Wang, T., Wang, Z., Liao, C., Wang, Z., Huang, R., Wang, D., Li, X., Wu, L., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20160844 · Cited by 372
Loss of TREM2 function increases amyloid seeding but reduces plaque-associated ApoE
Parhizkar, S., Arzberger, T., Brendel, M., Kleinberger, G., Deußing, M., Focke, C., Nuscher, B., Xiong, M., Ghasemigharagoz, A., Katzmarski, N., et al. (2019) · doi:10.7892/boris.125653 · Cited by 352
Immune Signaling in Neurodegeneration
Hammond, T. R., Marsh, S. E., & Stevens, B. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.016 · Cited by 336
Elucidating the Role of TREM2 in Alzheimer’s Disease
Ulrich, J. D., Ulland, T. K., Colonna, M., & Holtzman, D. M. (2017) · Neuron · doi:10.1016/j.neuron.2017.02.042 · Cited by 325
Otero, K., Turnbull, I. R., Poliani, P. L., Vermi, W., Cerutti, E., Aoshi, T., Tassi, I., Takai, T., Stanley, S. L., Miller, M., et al. (2009) · Nature Immunology · doi:10.1038/ni.1744 · Cited by 315
Phosphorylation of CARMA1 Plays a Critical Role in T Cell Receptor-Mediated NF-κB Activation
Matsumoto, R., Wang, D., Blonska, M., Li, H., Kobayashi, M., Pappu, B. P., Chen, Y., Wang, D., & Lin, X. (2005) · Immunity · doi:10.1016/j.immuni.2005.10.007 · Cited by 312
Piccio, L. M., Buonsanti, C., Cella, M., Tassi, I., Schmidt, R. E., Fenoglio, C., Rinker, J. R., Naismith, R. T., Panina‐Bordignon, P., Passini, N., et al. (2008) · Brain · doi:10.1093/brain/awn217 · Cited by 311
Amyloid Fibrils Activate Tyrosine Kinase-Dependent Signaling and Superoxide Production in Microglia
McDonald, D. R., Brunden, K. R., & Landreth, G. E. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-07-02284.1997 · Cited by 310
Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism
Song, W. M., Joshita, S., Zhou, Y., Ulland, T. K., Gilfillan, S., & Colonna, M. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20171529 · Cited by 305
The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E
Bailey, C. C., DeVaux, L. B., & Farzan, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.677286 · Cited by 303
Bemiller, S. M., McCray, T. J., Allan, K., Formica, S. V., Xu, G., Wilson, G., Kokiko-Cochran, O. N., Crish, S. D., Lasagna-Reeves, C. A., Ransohoff, R. M., et al. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0216-6 · Cited by 299
Song, W., Hooli, B., Mullin, K., Jin, S. C., Cella, M., Ulland, T. K., Wang, Y., Tanzi, R. E., & Colonna, M. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.07.004 · Cited by 297
Wunderlich, P., Glebov, K., Kemmerling, N., Tien, N. T., Neumann, H., & Walter, J. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.517540 · Cited by 296
TREM2 regulates microglial cell activation in response to demyelination in vivo
Cantoni, C., Bollman, B., Licastro, D., Xie, M., Mikesell, R., Schmidt, R., Yuede, C. M., Galimberti, D., Olivecrona, G., Klein, R. S., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1388-1 · Cited by 296
Beta amyloid oligomers and fibrils stimulate differential activation of primary microglia
Sondag, C. M., Dhawan, G., & Combs, C. K. (2009) · Journal of Neuroinflammation · doi:10.1186/1742-2094-6-1 · Cited by 295
TREM2-Ligand Interactions in Health and Disease
Kober, D. L., & Brett, T. J. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.04.004 · Cited by 284 · cited 1×
“It remains also possible that different TREM2 ligands may have different activities toward TREM2 signaling as previously postulated (Turnbull et al., 2006; Kober and Brett, 2017).”
BackgroundSchlepckow, K., Kleinberger, G., Fukumori, A., Feederle, R., Lichtenthaler, S. F., Steiner, H., & Haass, C. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707672 · Cited by 266
The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer's disease
Cheng-Hathaway, P. J., Reed-Geaghan, E. G., Jay, T. R., Casali, B. T., Bemiller, S. M., Puntambekar, S. S., von Saucken, V. E., Williams, R. Y., Karlo, J. C., Moutinho, M., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0262-8 · Cited by 252
The role of TREM2 in Alzheimer's disease and other neurodegenerative disorders
Carmona, S., Zahs, K., Wu, E., Dakin, K., Bras, J., & Guerreiro, R. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30232-1 · Cited by 244
TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria
N’Diaye, E.-N., Branda, C., Branda, S. S., Nevarez, L., Colonna, M., Lowell, C. A., Hamerman, J. A., & Seaman, W. E. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200808080 · Cited by 243
Kober, D. L., Alexander-Brett, J. M., Karch, C. M., Cruchaga, C., Colonna, M., Holtzman, M. J., & Brett, T. J. (2016) · eLife · doi:10.7554/elife.20391 · Cited by 238
Sayed, F. A., Telpoukhovskaia, M., Kodama, L., Li, Y., Zhou, Y., Le, D., Hauduc, A., Ludwig, C., Gao, F., Clelland, C., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811411115 · Cited by 229
Zhong, L., Wang, Z., Wang, D., Wang, Z., Martens, Y. A., Wu, L., Xu, Y., Wang, K., Li, J., Huang, R., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0247-7 · Cited by 222
Yuan, P., Condello, C., Keene, C. D., Wang, Y., Bird, T. D., Paul, S. M., Luo, W., Colonna, M., Baddeley, D., & Grutzendler, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.016 · Cited by 219
Thornton, P., Sevalle, J., Deery, M. J., Fraser, G., Zhou, Y., Ståhl, S., Franssen, E. H., Dodd, R. B., Qamar, S., Gomez Perez‐Nievas, B., et al. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707673 · Cited by 200
Feuerbach, D., Schindler, P. A., Barske, C., Joller, S., Beng-Louka, E., Worringer, K. A., Kommineni, S., Kaykas, A., Ho, D. J., Ye, C., et al. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.09.034 · Cited by 179
TREM2/DAP12 Signal Elicits Proinflammatory Response in Microglia and Exacerbates Neuropathic Pain
Kobayashi, M., Konishi, H., Sayo, A., Takai, T., & Kiyama, H. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1238-16.2016 · Cited by 164
TREM2 inhibits inflammatory responses in mouse microglia by suppressing the PI3K/NF‐κB signaling
Li, C., Zhao, B. Q., Lin, C., Gong, Z., & An, X. (2018) · Cell Biology International · doi:10.1002/cbin.10975 · Cited by 161
Accumulation of tau induced in neurites by microglial proinflammatory mediators
Gorlovoy, P., Larionov, S., Pham, T. T. H., & Neumann, H. (2009) · The FASEB Journal · doi:10.1096/fj.08-123877 · Cited by 156
High‐affinity interactions and signal transduction between Aβ oligomers and TREM2
Lessard, C. B., Malnik, S. L., Zhou, Y., Ladd, T. B., Cruz, P. E., Ran, Y., Chakrabaty, P., Mahan, T. E., Holtzman, D. M., Ulrich, J. D., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201809027 · Cited by 156
Zhong, L., Chen, X.-F., Zhang, Z.-L., Wang, Z., Shi, X.-Z., Xu, K., Zhang, Y.-W., Xu, H., & Bu, G. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.645986 · Cited by 133
Xie, Y., Guo, H., Wang, L., Xu, L., Zhang, X., Yu, L., Liu, Q., Li, Y., Zhao, N., Zhao, N., et al. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.11.004 · Cited by 123
Ren, M., Guo, Y., Wei, X., Yan, S., Qin, Y., Zhang, X., Jiang, F., & Lou, H. (2018) · Experimental Neurology · doi:10.1016/j.expneurol.2018.01.016 · Cited by 119
Alfonso, S. I., Callender, J. A., Hooli, B., Antal, C. E., Mullin, K., Sherman, M. A., Lesné, S. E., Leitges, M., Newton, A. C., Tanzi, R. E., et al. (2016) · Science Signaling · doi:10.1126/scisignal.aaf6209 · Cited by 103
Phorbol ester-stimulated NF-κB-dependent transcription: Roles for isoforms of novel protein kinase C
Holden, N. S., Squires, P. E., Kaur, M., Bland, R., Jones, C. E., & Newton, R. C. (2008) · Cellular Signalling · doi:10.1016/j.cellsig.2008.03.001 · Cited by 102
Jendresen, C., Årskog, V., Daws, M. R., & Nilsson, L. N. G. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0835-4 · Cited by 94
TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway
Zhong, L., Zhang, Z.-L., Li, X., Liao, C., Mou, P., Wang, T., Wang, Z., Wang, Z., Wei, M., Xu, H., et al. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00204 · Cited by 92
Park, J., Ji, I. J., An, H. J., Kang, M., Kang, S., Kim, D., & Yoon, S. (2015) · Traffic · doi:10.1111/tra.12264 · Cited by 90
Haure-Mirande, J.-V., Wang, M., Audrain, M., Fanutza, T., Kim, S. H., Heja, S., Readhead, B., Dudley, J. T., Blitzer, R. D., Schadt, E. E., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0255-6 · Cited by 84
TREM2 regulates innate immunity in Alzheimer’s disease
Li, J.-T., & Zhang, Y. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1148-y · Cited by 76
Inhibition of PKCδ reduces amyloid-β levels and reverses Alzheimer disease phenotypes
Du, Y., Zhao, Y., Li, C., Zheng, Q., Tian, J., Li, Z., Huang, T. Y., Zhang, W., & Xu, H. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171193 · Cited by 75
TREM2 expression in the human brain: a marker of monocyte recruitment?
Fahrenhold, M., Rakić, S., Classey, J. D., Brayne, C., Ince, P. G., Nicoll, J. A. R., Boche, D., & MRC‐CFAS (2017) · Brain Pathology · doi:10.1111/bpa.12564 · Cited by 74
Cell Type-Specific Regulation of ITAM-Mediated NF-κB Activation by the Adaptors, CARMA1 and CARD9
Hara, H., Ishihara, C., Takeuchi, A., Xue, L., Morris, S. W., Penninger, J. M., Yoshida, H., & Saito, T. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.2.918 · Cited by 68
Audrain, M., Haure-Mirande, J.-V., Wang, M., Kim, S. H., Fanutza, T., Chakrabarty, P., Fraser, P., St George-Hyslop, P. H., Golde, T. E., Blitzer, R. D., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0258-3 · Cited by 68
Anatabine lowers Alzheimer's Aβ production in vitro and in vivo
Paris, D., Beaulieu‐Abdelahad, D., Bachmeier, C. J., Reed, J. M., Ait‐Ghezala, G., Bishop, A., Chao, J., Mathura, V. S., Crawford, F., & MULLAN, M. J. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.09.019 · Cited by 65
Self-citationSo, T., Soroosh, P., Eun, S.-Y., Altman, A., & Croft, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008765108 · Cited by 61
Cerebrospinal Fluid Biomarkers, Education, Brain Volume, and Future Cognition
Roe, C. M., Fagan, A. M., Grant, E., Marcus, D. S., Benzinger, T. L. S., Mintun, M. A., Holtzman, D. M., & Morris, J. C. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.192 · Cited by 50
Park, J., Ji, I. J., Kim, D., An, H. J., & Yoon, S. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00618 · Cited by 48
CD13 mediates phagocytosis in human monocytic cells
Licona‐Limón, I., Garay-Canales, C. A., Muñoz-Paleta, O., & Ortega, E. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.2a0914-458r · Cited by 45
Sirkis, D. W., Aparicio, R. E., & Schekman, R. W. (2017) · Molecular Biology of the Cell · doi:10.1091/mbc.e17-06-0423 · Cited by 42
Zeng, K., Wang, S., Dong, X., Jiang, Y., Jin, H., & Tu, P. (2014) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2014.01.014 · Cited by 23
Varnum, M. M., Clayton, K. A., Yoshii-Kitahara, A., Yonemoto, G., Koro, L., Ikezu, S., & Ikezu, T. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.759159 · Cited by 22
Yu, S., Huang, H., Iliuk, A. B., Wang, W., Jayasundera, K. B., Tao, W. A., Post, C. B., & Geahlen, R. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.426130 · Cited by 18
Fırat, S. Ş., Temiz-Reşitoğlu, M., Güden, D. S., Şenol, Ş. P., Sari, A. N., Cil, M., Unsal, D., Korkmaz, B., Tunçtan, B., Malik, K. U., et al. (2018) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.13045 · Cited by 14
Haure‐Mirande, J., Wang, M., Audrain, M., Fanutza, T., Kim, S. H., Heja, S., Readhead, B., Dudley, J. T., Blitzer, R. D., Schadt, E. E., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0301-4 · Cited by 6
Daws (2001) · doi:10.1002/1521-4141(200103)31:3
Flagged first, then by citations
Cited by
Sorted by citations
TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways
Wang, S., Sudan, R., Peng, V., Zhou, Y., Du, S., Yuede, C. M., Lei, T., Hou, J., Cai, Z., Cella, M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.033 · Cited by 471
SYK coordinates neuroprotective microglial responses in neurodegenerative disease
Ennerfelt, H., Frost, E. L., Shapiro, D. A., Holliday, C., Zengeler, K. E., Voithofer, G., Bolte, A. C., Lammert, C. R., Kulas, J. A., Ulland, T. K., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.030 · Cited by 297
“Though previous in vitro studies have shown that TREM2 activation can provoke SYK signaling (Yao et al., 2019), it still remains to be seen whether TREM2 relies exclusively on SYK to coordinate its effects on in vivo Alzheimer’s-related disease progression.”
BackgroundTrem2 promotes foamy macrophage lipid uptake and survival in atherosclerosis
Patterson, M. T., Firulyova, M. M., Xu, Y., Hillman, H., Bishop, C., Zhu, A., Hickok, G. H., Schrank, P. R., Ronayne, C. E., Caillot, Z., et al. (2023) · Nature Cardiovascular Research · doi:10.1038/s44161-023-00354-3 · Cited by 204
AD-linked R47H- TREM2 mutation induces disease-enhancing microglial states via AKT hyperactivation
Sayed, F. A., Kodama, L., Fan, L., Carling, G. K., Udeochu, J. C., Le, D., Li, Q., Zhou, L., Wong, M. Y., Horowitz, R., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abe3947 · Cited by 155
Zhang, S., Zhu, L., Peng, Y., Zhang, L., Chao, F., Jiang, L. H., Xiao, Q., Liang, X., Tang, J., Yang, H., et al. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02401-5 · Cited by 143
Metadata
- Authors
- Yao, H., Coppola, K., Schweig, J. E., Crawford, F., Mullan, M., & Paris, D.
- Affiliations
- James A. Haley Veterans' Hospital (US)
- Corresponding author
- Yao, Hailan
- Venue
- Frontiers in Cellular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2019-10-10
- Volume
- 13
- Pages
- 457-457
- ISSN
- 1662-5102 (ISSN-L)
- PMC
- PMC6795686
- OpenAlex
- W2979963278
- Cited by
- 110
- References
- 86
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 21 · 2023: 17 · 2022: 17 · 2021: 13 · 2020: 6
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Veterans Affairs
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- TREM2, Alzheimer's disease, phagocytosis, NF-κB signaling, DAP12, Syk, apolipoprotein E, APOE ε4, PI3K/Akt signaling, phospholipase C-gamma, microglia, anti-inflammatory signaling, TNF-α
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.
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