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Regulation of Tau Pathology by the Microglial Fractalkine Receptor
Open accessAbstract
Aggregates of the hyperphosphorylated microtubule-associated protein tau (MAPT) are an invariant neuropathological feature of tauopathies. Here, we show that microglial neuroinflammation promotes MAPT phosphorylation and aggregation. First, lipopolysaccharide-induced microglial activation promotes hyperphosphorylation of endogenous mouse MAPT in nontransgenic mice that is further enhanced in mice lacking the microglial-specific fractalkine receptor (CX3CR1) and is dependent upon functional toll-like receptor 4 and interleukin-1 (IL-1) receptors. Second, humanized MAPT transgenic mice lacking CX3CR1 exhibited enhanced MAPT phosphorylation and aggregation as well as behavioral impairments that correlated with increased levels of active p38 MAPK. Third, in vitro experiments demonstrate that microglial activation elevates the level of active p38 MAPK and enhances MAPT hyperphosphorylation within neurons that can be blocked by administration of an interleukin-1 receptor antagonist and a specific p38 MAPK inhibitor. Taken together, our results suggest that CX3CR1 and IL-1/p38 MAPK may serve as novel therapeutic targets for human tauopathies.
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“Notably, we observed elevated levels of active (phosphorylated) p38α MAPK, but not GSK3β or regulators (p35/p25) of Cdk5, correlating with increased tau phosphorylation in the hippocampus of hTau mice deficient for the chemokine receptor CX3CR1 [22].”
From Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology (2016) · cites this paper as [22]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The p38α-mediated cytokine overproduction in microglia has been linked to inflammation-induced neurotoxicity in a variety of mouse models [22, 27–33].”
From Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology (2016) · cites this paper as [22]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“We have demonstrated recently that activated microglia induced tau hyperphosphorylation via activation of the p38α MAPK signaling pathway in the hTau mouse model of tauopathy [22, 23].”
From Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology (2016) · cites this paper as [22]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“As reported previously [22], exchange of 25% of the neuronal supernatant with Cx3cr1 –/– microglia CM led to an increase in tau phosphorylation on S199/S202 (AT8) and T231 (AT180) sites (Fig. 1d, e).”
From Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology (2016) · cites this paper as [22]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Furthermore, hyperphosphorylation of tau in this model was mediated by upregulation of p38α the MAPK pathway, but not GSK3β or CDK5 pathways [22].”
From Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology (2016) · cites this paper as [22]
Experimental — accuracy not yet measured
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In the citing paper
“Finally, accumulating evidence shows that microglia and monocytes play distinct roles in AD pathogenesis (116–119), thus implicating both the central and peripheral immune response in long-term outcome.”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [116]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Neuroinflammation is an early feature of pathophysiology in mouse models of tauopathy, where inflammatory changes precede the accumulation of aggregated tau (Yoshiyama et al., 2007) and pro-inflammatory molecules increase tau hyperphosphorylation and aggregation (Bhaskar et al., 2010).”
From Neuroinflammation and protein aggregation co-localize across the frontotemporal dementia spectrum (2020) · cites this paper as Bhaskar et al., 2010
The cited source says what the claim attributes to it.
In the citing paper
“As reported previously [22], a single injection of LPS led to AT8 and AT180 site tau phosphorylation in nontransgenic mice (Fig. 4b–d).”
From Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology (2016) · cites this paper as [22]
The cited source says what the claim attributes to it.
In the citing paper
“Our previous study suggested that enhancement of microglia-specific neuroinflammation via genetic deficiency of Cx3cr1 resulted in accelerated tau pathology and cognitive impairment in an hTau mouse model of tauopathy [22].”
From Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology (2016) · cites this paper as [22]
The cited source says what the claim attributes to it.
In the citing paper
“However, such complete deletion has also been associated with worsening memory deficits and tau pathology (28–31).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [28]
The cited source says what the claim attributes to it.
In the citing paper
“Similarly, deficiency of Cx3cr1 reduced amyloid deposition in two different APP models but aggravated tau hyperphosphorylation in hTau mice [65, 66].”
From Deletion of Abi3/Gngt2 influences age-progressive amyloid β and tau pathologies in distinctive ways (2022) · cites this paper as [65]
In the citing paper
“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 [137]
In the citing paper
“Bhaskar et al. reported that microglia activation induces tau hyperphosphorylation via the IL-1β/p38α MAPK pathway in vitro and in vivo [135, 137].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [137]
In the citing paper
“As mentioned above, p38α MAPK is a key kinase involved in microglia-induced neuroinflammation leading to tau pathology [135, 137], and this kinase can also directly regulate tau phosphorylation [39].”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [137]
In the citing paper
“the exacerbation of tau pathology in Cx3cr1 knockout mice was blocked with IL-1 antagonists (Bhaskar et al., 2010; Maphis et al., 2015)”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Bhaskar et al., 2010
In the citing paper
“Deleting the microglial protein Cx3cr1 in transgenic tau models showed that genetically enhanced microglial activation accelerated the onset and progression of tau pathology (Bhaskar et al., 2010; Maphis et al., 2015).”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Bhaskar et al., 2010
In the citing paper
“However, pretreating the neurons with an IL-1R antagonist attenuated the effects of CX3CR1−/− conditioned media”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [136]
In the citing paper
“Additionally, p38-MAPK levels were significantly increased in CX3CR1 deficient htau mice, though no changes were detected in GSK-3β or p25.”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [136]
In the citing paper
“thereby suggesting microglial-derived IL-1β promotes tau phosphorylation via p38-MAPK in neurons [136].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [136]
In the citing paper
“Genetic deletion of CX3CR1 in mice expressing human tau under its endogenous promoter (htau mice) led to substantially increased microglial activation indicated by CD68 staining as well as elevated levels of p-tau and insoluble tau aggregates [136].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [136]
In the citing paper
“The interaction between IL-1β driven neuroinflammation and neuronal tau hyperphosphorylation may be partially regulated by the microglial-specific fractalkine receptor (CX3CR1).”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [136]
In the citing paper
“However, it should be noted that IL-1β is not sufficient to cause neurotoxicity or neurodegeneration in the absence of tau [136, 138].”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [136]
In the citing paper
“the authors placed conditioned media from CX3CR1−/− microglia on wildtype neurons and observed comparable increases in p38-MAPK and p-tau.”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [136]
In the citing paper
“Endotoxin promotes amyloid β and tau aggregation and neuropathology”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [69]
In the citing paper
“and systemic endotoxin precipitates brain pathology in mice expressing prions [74], APP variants [33] or TAU variants [69] or mice with α-synuclein injected in the brain [46].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [69]
In the citing paper
“Endotoxin may also promote the production or aggregation of amyloid β [66–68], tau [68, 69] and α-synuclein [70, 71].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [69]
In the citing paper
“Microglia first sense and clear tau in an attempt to protect from tau toxicity, but dysregulation of microglial sensing and housekeeping pathways, such as the Cx3cr1 and Trem2 pathways, lead to dysregulation of the host-defense pathway, resulting in a neuroinflammatory response gone awry, causing neuronal damage and loss55–57.”
From Microglia in neurodegeneration (2018) · cites this paper as [55]
In the citing paper
“Genetic ablation of Cx3cl1396,397 or Cx3cr1389,398 in mouse models of tauopathy enhanced tau hyperphosphorylation, tau pathology, neuroinflammation, and cognitive deficits389,396–398 via IL-1/p38 MAPK pathway.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [389]
In the citing paper
“The deficiency of the CX3CR1 enhanced tau phosphorylation and aggregation and memory impairment in a transgenic mouse model of tauopathy in which the WT human MAPT gene replaced the endogenous mouse Mapt gene (hTau mice).389”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [389]
In the citing paper
“In patients with MAPT mutations, neuroinflammation may be triggered by the misfolding of mutant tau and contribute to its hyperphosphorylation and aggregation[4,14,16], while in C9orf72 and GRN cases, neuroinflammation could be triggered by dipeptide repeats or progranulin haploinsufficiency in advance of the large TDP-43 aggregates[14,17].”
From In vivo PET imaging of neuroinflammation in familial frontotemporal dementia (2021) · cites this paper as [16]
In the citing paper
“First, the proinflammatory cytokines TNFα, IL1 β, and IL6 have been shown to promote tau phosphorylation in neurons (Bhaskar et al., 2010; Kitazawa et al., 2011; Quintanilla et al., 2004).”
From Complement C3aR Inactivation Attenuates Tau Pathology and Reverses an Immune Network Deregulated in Tauopathy Models and Alzheimer’s Disease (2018) · cites this paper as Bhaskar et al., 2010
In the citing paper
“deleting the microglial cell-expressed homeostatic gene CX3C chemokine receptor 1(Cx3cr1) in htau mice [G] leads to amplified microglial activation and enhanced tau hyperphosphorylation/aggregation62,63”
From Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight (2018) · cites this paper as [62]
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Citations
Cites
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
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Jung, S., Aliberti, J., Graemmel, P., Sunshine, M. J., Kreutzberg, G. W., Sher, A., & Littman, D. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.11.4106-4114.2000 · Cited by 2,632 · cited 2×
“, 2006) as well as others (Jung et al., 2000) demonstrated that CX3CR1 deficiency alone does not lead to acute microglial activation or neurodegeneration.”
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
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Qin, L., Wu, X., Block, M. L., Liu, Y., Breese, G. R., Hong, J., Knapp, D. J., & Crews, F. T. (2007) · Glia · doi:10.1002/glia.20467 · Cited by 2,144 · cited 3×
“w) LPS doses and that the latter dose produced neurodegeneration and chronic microglial activation, which could be observed 10 months postinjection (Qin et al., 2007).”
InfluentialCuenda, A., Rouse, J., Doza, Y. N., Meier, R., Cohen, P., Gallagher, T. F., Young, P. R., & Lee, J. C. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00357-f · Cited by 2,086
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 · cited 7×
“Interestingly, our previous studies demonstrated that administration of LPS to Cx3cr1 / mice induces neurodegeneration that is also dependent upon IL-1 signaling (Cardona et al., 2006), suggesting that IL-1 may represent as an important signaling molecule between microglia and neurons.”
InfluentialSelf-citationHarrison, J. K., Jiang, Y., Chen, S., Xia, Y., Maciejewski, D., McNamara, R. K., Streit, W. J., Salafranca, M. N., Adhikari, S., Thompson, D. A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.18.10896 · Cited by 1,176 · cited 1×
“Notably, CX3CL1 is highly expressed in neurons while CX3CR1 is exclusively expressed in microglia within the CNS (Harrison et al., 1998).”
p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5
Tsai, L., Delalle, I., Caviness, V. S., Chae, T. H., & Harlow, E. (1994) · Nature · doi:10.1038/371419a0 · Cited by 923
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CX3CR1: a potential microglia-specific PET imaging target in Alzheimer’s and Parkinson’s diseases
Yang, H., Wang, Y., Xu, Y., & Wang, C. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1678159 · Cited by 6
Liu, R., Deng, Q., Gong, L., & Yang, L. (2026) · Neuroscience Bulletin · doi:10.1007/s12264-026-01598-2 · Cited by 5
“The sustained release of IL-1β creates a feed-forward loop by activating neuronal kinases, particularly p38 MAPK and glycogen synthase kinase-3β (GSK-3β) [223].”
Chen, W. W., Wang, L., Zhou, A. J., Fan, C., Zhang, Y. D., Wang, Z. P., Rong, S., & Wang, T. (2023) · Acta Alimentaria · doi:10.1556/066.2022.00230 · Cited by 5
“The excessive accumulation of Aβ peptide and the hyperphosphorylation of tau proteins trigger neuroinflammation, blood-brain barrier (BBB) dysfunction, and cognitive decline (Bhaskar et al., 2010; Nasaruddin et al., 2020).”
BackgroundAdenosine Receptors and Alzheimer’s Disease
Blum, D. L., Sandau, U. S., Laurent, C., Batalha, V. L., Leboucher, A., Hamdane, M., Pasquier, F., Boison, D., Buée, L., & Lopes, L. V. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3903-5_19 · Cited by 6
Therapeutic options for Progressive Supranuclear Palsy including investigational drugs
Shoeibi, A., & Litvan, I. (2017) · Expert Opinion on Orphan Drugs · doi:10.1080/21678707.2017.1335596 · Cited by 5
“This is further supported by studies on transgenic mice models that showed that microglial activation induces tau hyperphosphorylation through stimulation of the p38α MAPK-signaling pathway [98,99].”
BackgroundMixed dementia: the role of cerebrovascular pathology
Tabeeva, G. R. (2018) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro2018118091111 · Cited by 5
Analysis of Givinostat/ITF2357 Treatment in a Rat Model of Neonatal Hypoxic-Ischemic Brain Damage
Pawelec, P., Sypecka, J., Zalewska, T., & Ziemka‐Nałęcz, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158287 · Cited by 6
“Moreover, genetic ablation of the fractalkine receptor showed increased microglial activation in different models of inflammation [52,53].”
BackgroundThe role of inflammation in neurodegenerative diseases
Appel, S. H., Beers, D. R., & Zhao, W. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85654-6.00036-8 · Cited by 5
Role of Tau Protein Hyperphosphorylation in Diabetic Retinal Neurodegeneration
Mu, J., Zhang, Z., Jiang, C., Geng, H., & Duan, J. (2025) · Journal of Ophthalmology · doi:10.1155/joph/3278794 · Cited by 5
“In addition, the lack of the microglial division factor receptor CX3R1 may cause the microglia to take up and dissolve A β and TauOs, and the uptake of TauOs can further activate microglia to release infammatory factors and promote the vicious cycle of tau hyperphosphorylation [191, 192].”
Wolf, T., Moss, L. D., Hudson, C., Winters, A. M., Abdelmaboud, S. S., Avlas, M., Wohlfahrt, J., Guergues, J., Bickford, P. C., & Stevens, S. M. (2025) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.70034 · Cited by 4
Multifactorial glial responses and their contributions to Alzheimer's disease continuum
Hijioka, M., Manabe, T., & Saito, T. (2023) · Clinical and Experimental Neuroimmunology · doi:10.1111/cen3.12745 · Cited by 4
“Some reasoned alteration of cyclin-dependent kinase 5 and glycogen synthase kinase 3β activities at different ages of mice,(137,138) whereas others pointed to different kinases, such as p38 mitogen-activated protein kinase.(139) Importantly, the effects of sys-”
BackgroundRole of Inflammation in Neurodegenerative Diseases
Appel, S. H., Beers, D. R., & Zhao, W. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-398270-4.00025-2 · Cited by 4
Dadras, S., & Bhaskar, K. (2025) · ASN NEURO · doi:10.1080/17590914.2025.2598310 · Cited by 3
“We have previously demonstrated that LPS, which causes neuroinflammation through toll-like receptor-4 (TLR-4), can trigger tau phosphorylation in neurons (Bhaskar et al., 2010).”
InfluentialSelf-citationBrain and immune system: KURU disease a toxicological process?
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“By contrast, though extensive research shows CX3CL1-CX3CR1 is vital in regulating neurodegenerative diseases [21 – 24], in chronic degenerative conditions like ARHL, research on CX3CL1-CX3CR1 signaling is still scarce.”
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Microglia undergoes chemokine receptor, CX3CR1-mediated internalization of extracellular TauPreprint
Chidambaram, H., Desale, S. E., Suri, K., Murugan, N. A., & Chinnathambi, S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.03.626734 · Cited by 3
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Profiling the impact of different tau species on glial cell biology
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“This aligns with previous observations in both human tauopathies and animal models where fibrillar tau accumulation correlates with microglial activation and inflammatory cytokine production (Bhaskar et al., 2010; Ising et al., 2019; Hopp et al., 2018).”
Septyaningtrias, D. E., Sholikah, T. A., Suhda, S., Sumiwi, Y. A. A., & Susilowati, R. (2025) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-025-10245-y · Cited by 2
“However, other studies suggest that CX3CR1 downregulation may have detrimental consequences, including increased microglial activation (Bhaskar et al. 2010 ), impaired tau clearance (Bolós et al. 2017), and increased aggregation of tau and amyloid beta (Bhaskar et al. 2010; Puntambekar et al. 2022…”
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Thanos, J. M., Campbell, O. C., Natale, N. R., Marco, A. R., Puchalski, M. A., & Lukens, J. R. (2026) · Cells · doi:10.3390/cells15070591 · Cited by 2
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“Pro-inflammatory mediators including TNF-α , IL-1 β , IL-6, and complement components can promote tau phosphorylation and exacerbate neuronal dysfunction (Bhaskar et al., 2010; Kitazawa et al., 2011; Kahlson and Colodner, 2015).”
Laurent, C., Dorothée, G., Hunot, S., Martin, E., Delarasse, C., Buée, L., & Blum, D. L. (2017) · médecine/sciences · doi:10.1051/medsci/20173310002 · Cited by 2
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“Paradoxically, microglial C-X3-C motif chemokine receptor 1 (CX3CR1) disruption has been shown to exacerbate tau deposition whilst enhancing the phagocytic ability of microglial against A β deposition [22,62,66–71].”
BackgroundHushmandi, K., Reiter, R. J., Farahani, N., Cho, W. C. S., Alimohammadi, M., & Khoshnazar, S. M. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111325 · Cited by 2
In Search of Therapeutic Solutions for Alzheimer’s Disease
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“This finding suggests that CX3CR1 and IL-1/p38 MAPK pathway may serve as novel therapeutic target for human tauopathies (Bhaskar et al., 2010, Cho et al., 2011).”
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“This relationship may exist since there is evidence to support that activated microglia is involved in tau phosphorylation and, perhaps, tau aggregation through interleukin1 (IL1)/p38 mitogen-activated protein kinases (MAPK) signaling (Bhaskar et al., 2010).”
BackgroundResearch progress of microglial surface receptors in perioperative neurocognitive disorders
Tang, C., Liu, D., & Zhu, Z. (2023) · Ibrain · doi:10.1002/ibra.12136 · Cited by 2
“86 Under physiological conditions, disruption of CX3CR1 signaling through increased action of IL ‐ 1 β leads to impaired cognitive function and synaptic plasticity, 87 suggesting that CX3CR1 plays an important role in maintaining central nervous system homeostasis and normal interneuronal…”
Vasconcelos, B., Bird, M., Stancu, I., Terwel, D., & Dewachter, I. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-805120-7.00006-3 · Cited by 2
Impaired Signaling of NF-κB and NRF2 in CX3CR1-Deficient Microglia: Implications in TauopathiesPreprint
Castro‐Sánchez, S., García‐Yagüe, Á. J., Kügler, S., & Lastres‐Becker, I. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/346304 · Cited by 2
Hassan-Abdi, R., Brenet, A., Bennis, M., Yanicostas, C., & Soussi‐Yanicostas, N. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/731901 · Cited by 2
CX3CL1 intracellular domain and adult neurogenesis
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Metadata
- Authors
- Bhaskar, K., Konerth, M., Kokiko-Cochran, O. N., Cardona, A., Ransohoff, R. M., & Lamb, B. T.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Lamb, Bruce T.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 68
- Issue
- 1
- Pages
- 19-31
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2950825
- OpenAlex
- W2153206087
- Cited by
- 639
- References
- 49
- Citations by year
- 2026: 31 · 2025: 36 · 2024: 36 · 2023: 55 · 2022: 69 · 2021: 50 · 2020: 43 · 2019: 51 · 2018: 48 · 2017: 44 · 2016: 28 · 2015: 38 · 2014: 38 · 2013: 29 · 2012: 20
- FWCI
- 15.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1020 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Dana Foundation
- National Multiple Sclerosis Society
- CurePSP
- Alzheimer's Association
- National Institutes of Health (AG023012)
- American Health Assistance Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- tau hyperphosphorylation, tau aggregation, tauopathy, microglial activation, neuroinflammation, TLR4, interleukin-1 receptor, p38 MAPK, lipopolysaccharide, therapeutic target
- MeSH terms
- CX3C Chemokine Receptor 1, CD68 Molecule, Analysis of Variance, Animals, Animals, Newborn, Cell Count, Cells, Cultured, Disease Models, Animal, Enzyme Inhibitors, Gene Expression Regulation, Humans, Imidazoles, Lipopolysaccharides, Mice, Inbred C57BL, Models, Biological, Neurons, Phosphorylation, Pyridines, Time Factors, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Silver Staining, tau Proteins, Culture Media, Conditioned, Receptors, Interleukin-1, Microglia, Mice, Knockout, Statistics, Nonparametric, Maze Learning, Coculture Techniques, Receptors, Chemokine, Tauopathies, p38 Mitogen-Activated Protein Kinases, Toll-Like Receptor 4, Mice
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