Activated CX3CL1/Smad2 Signals Prevent Neuronal Loss and Alzheimer's Tau Pathology-Mediated Cognitive Dysfunction
Open accessAbstract
Neurofibrillary tangles likely cause neurodegeneration in Alzheimer's disease (AD). We demonstrate that the CX3CL1 C-terminal domain can upregulate neurogenesis, which may ameliorate neurodegeneration. Here we generated transgenic (Tg-CX3CL1) mice by overexpressing CX3CL1 in neurons. Tg-CX3CL1 mice exhibit enhanced neurogenesis in both subgranular and subventricular zones. This enhanced neurogenesis correlates well with elevated expression of TGF-β2 and TGF-β3, and activation of their downstream signaling molecule Smad2. Intriguingly, the enhanced adult neurogenesis was mitigated when Smad2 expression was deleted in neurons, supporting a role for the CX3CL1–TGF-β2/3–Smad2 pathway in the control of adult neurogenesis. When Tg-CX3CL1 mice were crossed with Alzheimer's PS19 mice, which overexpress a tau P301S mutation and exhibit age-dependent neurofibrillary tangles and neurodegeneration, overexpressed CX3CL1 in both male and female mice was sufficient to rescue the neurodegeneration, increase survival time, and improve cognitive function. Hence, we provide in vivo evidence that CX3CL1 is a strong activator of adult neurogenesis, and that it reduces neuronal loss and improves cognitive function in AD. SIGNIFICANCE STATEMENT This study will be the first to demonstrate that enhanced neurogenesis by overexpressed CX3CL1 is mitigated by disruption of Smad2 signaling and is independent of its interaction with CX3CR1. Overexpression of CX3CL1 lengthens the life span of PS19 tau mice by enhancing adult neurogenesis while having minimal effect on tau pathology. Enhancing neuronal CX3CL1, mainly the C-terminal fragment, is a therapeutic strategy for blocking or reversing neuronal loss in Alzheimer's disease or related neurodegenerative disease patients.
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Fractalkine upregulation reduces tau pathology and neurodegeneration in an animal model, and elevated plasma fractalkine levels were protective in a stroke population.
“upregulation of fractalkine, a chemokine that dampens the pro-inflammatory state of microglia and plays a role in adult neurogenesis, has been shown to reduce tau pathology and neurodegeneration in an animal model [57], and elevated plasma fractalkine levels were protective in a stroke population [58].”
From Evaluation of exploratory fluid biomarkers from a phase 1 senolytic trial in mild Alzheimer's disease (2025) · cites this paper as [57]
The Results section reports that CX3CL1 overexpression partially rescued neuronal loss in PS19 tau mice, but did not significantly change measured tau levels. The Discussion likewise says it prevented or reduced neurodegeneration without an obvious reduction in tau pathology. The plasma fractalkine finding is attributed to a different citation [58] and is not assessed here. (LLM, conf=0.94)
Experimental — accuracy not yet measuredDeletion of CX3CR1 or depression of the CX3CL1/CX3CR1 axis reduces Aβ deposition but exacerbates tau pathology, such as increased phosphorylation and aggregation of tau, and this is associated with worsened behavioral and cognitive impairments.
“Deletion of CX3CR1 or depression of the CX3CL1/CX3CR1 axis reduces Aβ deposition [130–132] but exacerbates tau pathology, such as increased phosphorylation and aggregation of tau, and this is associated with worsened behavioral and cognitive impairments [132–137] (Fig. 1).”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [136]
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Cites
Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus
Shi, Y., & Massagué, J. (2003) · Cell · doi:10.1016/s0092-8674(03)00432-x · Cited by 5,860 · see citing works
The novel object recognition memory: neurobiology, test procedure, and its modifications
Antunes, M., & Biala, G. (2012) · Cognitive Processing · doi:10.1007/s10339-011-0430-z · Cited by 2,390 · see citing works
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 · see citing works
A new class of membrane-bound chemokine with a CX3C motif
Bazan, J. F., Bacon, K. B., Hardiman, G., Wang, W., Soo, K., Rossi, D., Greaves, D. R., Zlotnik, A., & Schall, T. J. (1997) · Nature · doi:10.1038/385640a0 · Cited by 2,013 · see citing works
Control of microglial neurotoxicity by the fractalkine receptor
Cardona, A. E., Pioro, E. P., Sasse, M. E., Kostenko, V., Cardona, S. M., Dijkstra, I. M., Huang, D., Kidd, G., Dombrowski, S., Dutta, R., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1715 · Cited by 1,531 · see citing works
Imai, T., Hieshima, K., Haskell, C. A., Baba, M., Nagira, M., Nishimura, M., Kakizaki, M., Takagi, S., Nomiyama, H., Schall, T. J., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80438-9 · Cited by 1,446 · see citing works
Bevins, R. A., & Besheer, J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.205 · Cited by 1,278 · see citing works
Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior
Gonçalves, J. T., Schafer, S. T., & Gage, F. H. (2016) · Cell · doi:10.1016/j.cell.2016.10.021 · Cited by 1,122 · see citing works
Borchelt, D. R., Ratovitski, T., van Lare, J., Lee, M. K., Gonzales, V., Jenkins, N. A., Copeland, N. G., Price, D. L., & Sisodia, S. S. (1997) · Neuron · doi:10.1016/s0896-6273(00)80974-5 · Cited by 1,023 · see citing works
Yang, X. Y., Letterio, J. J., Lechleider, R. J., Chen, L., Hayman, R., Gu, H., Roberts, A. B., & Deng, C. (1999) · The EMBO Journal · doi:10.1093/emboj/18.5.1280 · Cited by 889 · see citing works
Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation
Pan, Y., Lloyd, C. M., Zhou, H., Dolich, S., Deeds, J., Gonzalo, J.-Á., Vath, J., Gosselin, M., Ma, J., Dussault, B. J., et al. (1997) · Nature · doi:10.1038/42491 · Cited by 643 · see citing works
Regulation of Tau Pathology by the Microglial Fractalkine Receptor
Bhaskar, K., Konerth, M., Kokiko-Cochran, O. N., Cardona, A., Ransohoff, R. M., & Lamb, B. T. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.023 · Cited by 639 · see citing works
Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer’s Disease Patients
Tobin, M. K., Musaraca, K., Disouky, A., Shetti, A., Bheri, A., Honer, W. G., Kim, N., Dawe, R. J., Bennett, D. A., Arfanakis, K., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.05.003 · Cited by 603 · see citing works
Smad2 role in mesoderm formation, left–right patterning and craniofacial development
Nomura, M., & Li, E. (1998) · Nature · doi:10.1038/31693 · Cited by 597 · see citing works
Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease
Fuhrmann, M., Bittner, T., Jung, C. K. E., Burgold, S., Page, R. M., Mitteregger, G., Haass, C., LaFerla, F. M., Kretzschmar, H., & Herms, J. (2010) · Nature Neuroscience · doi:10.1038/nn.2511 · Cited by 562 · see citing works
Lee, S., Varvel, N. H., Konerth, M. E., Xu, G., Cardona, A. E., Ransohoff, R. M., & Lamb, B. T. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.100265 · Cited by 539 · cited 2× · see citing works
“Deficiency in CX3CR1 may reduce amyloid deposition in AD mouse models overexpressing mutant APP or APP/PS1 (Lee et al., 2010) and prevents neuronal loss in a 3XTg AD mouse model overexpressing mutant APP/PS1/tau (Fuhrmann et al.”
BackgroundDatto, M., Frederick, J. P., Pan, L., Borton, A. J., Zhuang, Y., & Wang, X. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.4.2495 · Cited by 472 · see citing works
Diagnostic Criteria for Neuropathologic Assessment of Alzheimer’s Disease
Braak, H., & Braak, E. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00062-6 · Cited by 410 · see citing works
Glial contributions to neurodegeneration in tauopathies
Leyns, C. E. G., & Holtzman, D. M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0192-x · Cited by 409 · see citing works
Fractalkine and CX3CR1 regulate hippocampal neurogenesis in adult and aged rats
Bachstetter, A. D., Morganti, J. M., Jernberg, J., Schlunk, A., Mitchell, S. H., Brewster, K. W., Hudson, C. E., Cole, M. J., Harrison, J. K., Bickford, P. C., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.11.022 · Cited by 364 · see citing works
Fractalkine regulation of microglial physiology and consequences on the brain and behavior
Paolicelli, R. C., Bisht, K., & Tremblay, M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00129 · Cited by 314 · see citing works
Weinstein, M. B., Yang, X. Y., Li, C., Xu, X., Gotay, J., & Deng, C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.16.9378 · Cited by 300 · see citing works
Cho, S.-H., Sun, B., Zhou, Y., Kauppinen, T. M., Halabisky, B., Wes, P., Ransohoff, R. M., & Gan, L. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.254268 · Cited by 268 · see citing works
Hughes, P. M., Botham, M. S., Frentzel, S., Mir, A., & Perry, V. H. (2002) · Glia · doi:10.1002/glia.10037 · Cited by 252 · see citing works
Fractalkine and fractalkine receptors in human neurons and glial cells
Hatori, K., Nagai, A., Heisel, R., Ryu, J. K., & Kim, S. U. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10304 · Cited by 232 · see citing works
Absence of CX3CR1 impairs the internalization of Tau by microglia
Bolós, M., Llorens-Martín, M., Perea, J. R., Jurado-Arjona, J., Rábano, A., Hernández, F., & Avila, J. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0200-1 · Cited by 231 · see citing works
Modulating neurotoxicity through CX3CL1/CX3CR1 signaling
Limatola, C., & Ransohoff, R. M. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00229 · Cited by 210 · see citing works
Intersection of pathological tau and microglia at the synapse
Vogels, T., Murgoci, A.-N., & Hromádka, T. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0754-y · Cited by 197 · see citing works
Functions of mammalian Smad genes as revealed by targeted gene disruption in mice
Weinstein, M., Yang, X. Y., & Deng, C. (2000) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(99)00028-3 · Cited by 173 · see citing works
Deletion of Smad2 in Mouse Liver Reveals Novel Functions in Hepatocyte Growth and Differentiation
Ju, W., Ogawa, A., Heyer, J., Nierhof, D., Yu, L., Kucherlapati, R., Shafritz, D. A., & Böttinger, E. P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.26.2.654-667.2006 · Cited by 153 · see citing works
Hollands, C., Tobin, M. K., Hsu, M., Musaraca, K., Yu, T., Mishra, R., Kernie, S. G., & Lazarov, O. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0207-7 · Cited by 144 · see citing works
Hu, X., Das, B., Hou, H., He, W., & Yan, R. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171831 · Cited by 127 · see citing works
Self-citationOpposing Effects of Membrane-Anchored CX3CL1 on Amyloid and Tau Pathologies via the p38 MAPK Pathway
Lee, S., Xu, G., Jay, T. R., Bhatta, S., Kim, K.-W., Jung, S., Landreth, G. E., Ransohoff, R. M., & Lamb, B. T. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0853-14.2014 · Cited by 123 · see citing works
Guedes, J. R., Lao, T., Cardoso, A. L., & El Khoury, J. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00549 · Cited by 115 · see citing works
Fractalkine in the nervous system: neuroprotective or neurotoxic molecule?
Lauro, C., Catalano, M., Trettel, F., & Limatola, C. (2015) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12805 · Cited by 114 · see citing works
Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy
Nash, K. R., Lee, D. C., Hunt, J. B., Morganti, J. M., Selenica, M.-L., Moran, P., Reid, P., Brownlow, M., Guang-Yu Yang, C., Savalia, M., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.011 · Cited by 108 · see citing works
Hulshof, S. C. J., van Haastert, E. S., Kuipers, H. F., van den Elsen, P. J., Groot, C. J. A. D., van der Valk, P., Ravid, R., & Biber, K. P. H. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.9.899 · Cited by 93 · see citing works
Ultrastructure and Function of the Fractalkine Mucin Domain in CX3C Chemokine Domain Presentation
Fong, A. M., Erickson, H., Zachariah, J. P., Poon, S., Schamberg, N. J., Imai, T., & Patel, D. D. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.6.3781 · Cited by 89 · see citing works
BACE1 Regulates Hippocampal Astrogenesis via the Jagged1-Notch Pathway
Hu, X., He, W., Luo, X., Tsubota, K. E., & Yan, R. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.06.005 · Cited by 86 · see citing works
Self-citationWang, H., Li, Y., Ryder, J. W., Hole, J. T., Ebert, P. J., Airey, D. C., Qian, H.-R., Logsdon, B., Fisher, A., Ahmed, Z., et al. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0296-y · Cited by 83 · see citing works
Luo, X., He, W., Hu, X., & Yan, R. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.09.026 · Cited by 52 · see citing works
Self-citationThe intracellular domain of CX3CL1 regulates adult neurogenesis and Alzheimer’s amyloid pathology
Fan, Q., Gayen, M., Singh, N., Gao, F., He, W., Hu, X., Tsai, L., & Yan, R. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20182238 · Cited by 52 · see citing works
Self-citationGeneration of novel conditional and hypomorphic alleles of the Smad2 gene
Liu, Y., Festing, M. H., Hester, M. E., Thompson, J. C., & Weinstein, M. B. (2004) · genesis · doi:10.1002/gene.20072 · Cited by 32 · see citing works
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Chen, Y., & Yu, Y. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02853-3 · Cited by 516 · see citing works
Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220 · see citing works
CX3CL1/CX3CR1 signaling targets for the treatment of neurodegenerative diseases
Subbarayan, M. S., Joly‐Amado, A., Bickford, P. C., & Nash, K. R. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107989 · Cited by 204 · see citing works
Microglia in Alzheimer’s Disease in the Context of Tau Pathology
Perea, J. R., Bolós, M., & Ávila, J. (2020) · Biomolecules · doi:10.3390/biom10101439 · Cited by 127 · see citing works
Puntambekar, S. S., Moutinho, M., Lin, P. B.-C., Jadhav, V., Tumbleson-Brink, D., Balaji, A., Benito, M. A., Xu, G., Oblak, A., Lasagna-Reeves, C. A., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00545-9 · Cited by 113 · see citing works
Role of Chemokines in the Development and Progression of Alzheimer’s Disease
Wojcieszak, J., Kuczyńska, K., & Zawilska, J. B. (2022) · Journal of Molecular Neuroscience · doi:10.1007/s12031-022-02047-1 · Cited by 97 · see citing works
Physical Exercise-Induced Myokines in Neurodegenerative Diseases
Lee, B., Shin, M., Park, Y., Won, S.-Y., & Cho, K. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115795 · Cited by 79 · see citing works
Alzheimer’s genes in microglia: a risk worth investigating
Sudwarts, A., & Thinakaran, G. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00679-4 · Cited by 46 · see citing works
The effect of aged microglia on synaptic impairment and its relevance in neurodegenerative diseases
Triviño, J. J., & von Bernhardi, R. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.104982 · Cited by 43 · see citing works
Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease
Gu, X., Lai, D., Liu, S., Chen, K., Zhang, P., Chen, B., Huang, G., Cheng, X., & Lu, C. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.949083 · Cited by 40 · see citing works
Critical Molecular and Cellular Contributors to Tau Pathology
Song, L., Wells, E. A., & Robinson, A. S. (2021) · Biomedicines · doi:10.3390/biomedicines9020190 · Cited by 36 · see citing works
TGF-β Signaling in Microglia: A Key Regulator of Development, Homeostasis and Reactivity
Li, L., Sun, B., Harris, O. A., & Luo, J. (2024) · Biomedicines · doi:10.3390/biomedicines12112468 · Cited by 38 · see citing works
Rodriguez, D., Church, K. A., Pietramale, A. N., Cardona, S. M., Vanegas, D., Rorex, C., Leary, M. C., Muzzio, I. A., Nash, K. R., & Cardona, A. E. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02983-8 · Cited by 37 · see citing works
Donison, N. S., Palik, J., Volkening, K., & Strong, M. J. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00842-z · Cited by 39 · see citing works
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Bivona, G., Iemmolo, M., & Ghersi, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098230 · Cited by 35 · see citing works
Huang, X., Wang, Y., & Xiang, Y. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.104263 · Cited by 31 · see citing works
Banerjee, J., Dorfman, M. D., Fasnacht, R. D., Douglass, J. D., Wyse‐Jackson, A. C., Barría, A., & Thaler, J. P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126380 · Cited by 23 · see citing works
Phosphodiesterase-4 Inhibition in Parkinson’s Disease: Molecular Insights and Therapeutic Potential
Roy, D., Balasubramanian, S., Krishnamurthy, P. T., Sola, P., & Rymbai, E. (2023) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-023-01349-1 · Cited by 24 · see citing works
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Johnson, A. M., & Lukens, J. R. (2023) · European Journal of Immunology · doi:10.1002/eji.202250266 · Cited by 20 · see citing works
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Bettinetti‐Luque, M., Trujillo‐Estrada, L., García‐Fuentes, E., Andreo‐Lopez, J., Sanchez-Varo, R. M., Garrido‐Sánchez, L., Mediavilla, A. G., López, M. G., García‐Caballero, M., Gutiérrez, A., et al. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16243 · Cited by 21 · see citing works
Garbarino, V. R., Palavicini, J. P., Melendez, J., Barthelemy, N. R., He, Y., Kautz, T. F., Lopez-Cruzan, M., Mathews, J. J., Xu, P., Zhang, B., et al. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00591 · Cited by 19 · see citing works
“…of fractalkine, a chemokine that dampens the pro-in fl ammatory state of microglia and plays a role in adult neurogenesis, has been shown to reduce tau pathology and neurodegeneration in an animal model [57], and elevated plasma fractalkine levels were protective in a stroke population [58].”
Reelin changes hippocampal learning in aging and Alzheimer’s disease
Marckx, A. T., Fritschle, K., Calvier, L., & Herz, J. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113482 · Cited by 19 · see citing works
Kim, H. S., Shin, S. M., Kim, S., Nam, Y., Yoo, A., & Moon, M. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1002281 · Cited by 19 · see citing works
Microglia Biomarkers in Alzheimer’s Disease
Zhang, P., Hu, H., Tan, L., & Yu, J. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02348-3 · Cited by 18 · see citing works
Sirkis, D. W., Solsberg, C. W., Johnson, T. P., Bonham, L. W., Sturm, V. E., Lee, S. E., Rankin, K. P., Rosen, H. J., Boxer, A. L., Seeley, W. W., et al. (2023) · Genome Medicine · doi:10.1186/s13073-023-01205-3 · Cited by 17 · see citing works
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Gutiérrez, I. L., Martín‐Hernández, D., MacDowell, K. S., García‐Bueno, B., Caso, J. R., Leza, J. C., & Madrigal, J. L. M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26030959 · Cited by 17 · see citing works
Role of the CX3CL1-CX3CR1 axis in renal disease
Hamdan, D., & Robinson, L. A. (2021) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00059.2021 · Cited by 17 · see citing works
Ribeiro, R., Silva, E. G., Moreira, F., Gomes, G. F., Cussat, G. R., Silva, B. R. C., da Silva, M. C. M., Fernandes, H. D. B., Oliveira, C. D. S., Guarnieri, L. D. O., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-42955-9 · Cited by 10 · see citing works
Alves, R. L., Gonçalves, A., Voytyuk, I., & Harrison, D. C. (2025) · Experimental Neurology · doi:10.1016/j.expneurol.2025.115234 · Cited by 12 · see citing works
Wang, B., Sun, X., Wang, J., Deng, X., Lin, Y., Liu, F., Dong, R., Lin, X., & Bi, Y. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.772795 · Cited by 10 · see citing works
Gayen, M., Benoit, M., Fan, Q., Hudobenko, J., & Yan, R. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102532 · Cited by 10 · see citing works
Self-citationPolyserine-mediated targeting of FAF2/UBXD8 ameliorates tau aggregation
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Orr, M. E., Garbarino, V. R., Palavicini, J., Melendez, J., Barthélemy, N. R., He, Y., Kautz, T. F., Lopez‐Cruzan, M., Mathews, J. J., Xu, P., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-3994894/v1 · Cited by 8 · see citing works
Spicer, M. M., Yang, J., Fu, D., DeVore, A. N., Lauffer, M., Sayar, N., Atasoy, D., & Fisher, R. A. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01993 · Cited by 9 · see citing works
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Chen, Y., Liu, J., Zhang, S., Gao, M., Wang, F., Cai, M., Lu, C., Li, S. A., & Zhao, J. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1696689 · Cited by 7 · see citing works
Tang, J., Qi, F., Zou, J., Liu, H., Zuo, Z., Wang, L., Wang, N., Li, Z., Kumar, A., Guo, K., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-08691-8 · Cited by 6 · see citing works
Paul, D., & Basavan, D. (2022) · Future Journal of Pharmaceutical Sciences · doi:10.1186/s43094-022-00446-0 · Cited by 5 · see citing works
He, Q., Zhou, T., & He, Q. (2025) · Brain Sciences · doi:10.3390/brainsci15070759 · Cited by 5 · see citing works
ZHAO, J.-F., JIANG, Y.-R., GUO, T.-L., JIAO, Y.-Q., & WANG, X. (2024) · Biocell · doi:10.32604/biocell.2024.050120 · Cited by 4 · see citing works
MAIT cell deficiency exacerbates neuroinflammation in P301S human tau transgenic mice
Zhang, Y., Yang, Z., Jiang, N., Tan, X., Jiang, P., Cao, G., & Yang, Q. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03413-7 · Cited by 3 · see citing works
Vastrad, B. M., & Vastrad, C. M. (2025) · Genome Instability & Disease · doi:10.1007/s42764-025-00158-8 · Cited by 2 · see citing works
Nixon, A. G., Hong, N. S., Agha, B. M., Ham, J. R., Monteith, M., Kaloa, T., Kyriazopolus, A., Nielsen, M., Robertson, D. R., Golubov, A., et al. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261421654 · Cited by 1 · see citing works
Bang-feng, L., Chen, X., Xie, R., Mo, Y.-F., Wu, Y.-Z., Meng, Y., Han, X.-L., Chen, M., & Peng, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1818802 · Cited by 2 · see citing works
Effect of Fractalkine Signaling on Neuroinflammation and Neuropathic Pain–like Behavior in Mice
Fan, Q., Kim, J., Zhang, J., Zhang, Q., Hwang, M., Li, J., Li, F., Yin, Y., Han, Y., Shah, K., et al. (2026) · Anesthesiology · doi:10.1097/aln.0000000000006257 · Cited by 1 · see citing works
Self-citationСахаров, А. В., Мындускин, И. В., & Терешков, П. П. (2020) · Сибирский вестник психиатрии и наркологии · doi:10.26617/1810-3111-2020-4(109)-15-20 · Cited by 1 · see citing works
Wang, B., Sun, J., He, T., Deng, Y. X., Lin, N., Liu, H. F., Lin, X., Dong, R., Liu, Q. Y., & Bi, Y.-L. (2021) · Research Square · doi:10.21203/rs.3.rs-138907/v1
Wang, B., Lin, X., Sun, X., Liu, F. H., He, T., Deng, X., Lin, Y., Dong, R., & Bi, Y. (2021) · Research Square · doi:10.21203/rs.3.rs-420209/v1
Mendiola, A. S., Church, K. A., Cardona, S. M., Vanegas, D., Garcia, S. A., Macklin, W. B., Lira, S. A., Ransohoff, R. M., Kokovay, E., Lin, C. A., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.06.447262
Sirkis, D. W., Solsberg, C. W., Johnson, T. P., Bonham, L. W., Sturm, V. E., Lee, S. E., Rankin, K. P., Rosen, H. J., Boxer, A. L., Seeley, W. W., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.28.514304
Exploration of C-terminal CX3CL1 for reducing age-dependent neurodegeneration
Hudobenko, J., Gayen, M., Benoit, M., Singh, N. K., & Yan, R. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.373702
Self-citationQi, F., & Yao, Z. (2024) · Research Square · doi:10.21203/rs.3.rs-3831042/v1
Liu, F., Tang, J., Zou, J., Liu, H., Zuo, Z., Wang, L., Wang, N., Li, Z., Kumar, A., Guo, K., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.03.601972
Ananathanarayana, V., Upadhyay, R., Illanad, G. H., Krishnan, D., Bochageri, N. P., Sevanan, M., Bagewadi, Z., Sivasamy, R., & Chinnathambi, S. (2025) · Advances in immunology · doi:10.1016/bs.ai.2025.11.002
Rodriguez, D., Church, K. A., Pietramale, A. N., Cardona, S. M., Vanegas, D., Rorex, C., Leary, M. C., Muzzio, I. A., Nash, K. R., & Cardona, A. E. (2024) · Figshare · doi:10.6084/m9.figshare.25143609
Puntambekar, S. S., Moutinho, M., Lin, P. B., Jadhav, V., Tumbleson, D. M., Balaji, A., Benito, M. A., Xu, G., Oblak, A. L., Lasagna‐Reeves, C. A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20175603
Puntambekar, S. S., Moutinho, M., Lin, P. B., Jadhav, V., Tumbleson, D. M., Balaji, A., Benito, M. A., Xu, G., Oblak, A. L., Lasagna‐Reeves, C. A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20175579
Puntambekar, S. S., Moutinho, M., Lin, P. B., Jadhav, V., Tumbleson, D. M., Balaji, A., Benito, M. A., Xu, G., Oblak, A. L., Lasagna‐Reeves, C. A., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20175606
Chemokines in Alzheimer's Disease: Early Defence, Late Damage and the Impact of Sex and Infection
Aldana, B. I., & Freude, K. (2026) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.70273
- Authors
- Fan, Q., He, W., Gayen, M., Benoit, M. R., Luo, X., Hu, X., & Yan, R.
- Affiliations
- Cleveland Clinic (US)
- UConn Health (US)
- Corresponding author
- Yan, Riqiang
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2019-12-10
- Volume
- 40
- Issue
- 5
- Pages
- 1133-1144
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6989010
- OpenAlex
- W2995210504
- Cited by
- 58
- References
- 43
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 8 · 2023: 9 · 2022: 13 · 2021: 11 · 2020: 2
- FWCI
- 4.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG025493, RF1AG046929, RF1AG058261, RF1AG025493, R01 AG058261, R01AG046929)
- National Institute of Neurological Disorders and Stroke (RF1NS074256, R01NS074256)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- fractalkine, Smad2, TGF-beta2, TGF-beta3, adult neurogenesis, Alzheimer's disease, tau pathology, neurofibrillary tangles, neuronal loss, cognitive impairment, PS19 mice, neurodegeneration, subventricular zone, subgranular zone
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Female, Male, Mice, Transgenic, Neurons, tau Proteins, Smad2 Protein, Chemokine CX3CL1, Neurogenesis, Spatial Memory
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