The DOI matches its Crossref record; 249 of the 255 references it cites were found in a registry or an index.
Toll-like receptors in the pathogenesis of neuroinflammation
Abstract
Toll-like receptors (TLRs) are discovered as crucial pattern recognition receptors (PRRs) involved in the recognition of pathogen-associated molecular patterns (PAMPs). Later studies showed their involvement in the recognition of various damage/danger-associated molecular patterns (DAMPs) generated by host itself. Thus, TLRs are capable of recognizing wide-array of patterns/molecules derived from pathogens and host as well and initiating a proinflammatory immune response through the activation of NF-κB and other transcription factors causing synthesis of proinflammatory molecules. The process of neuroinflammation is seen under both sterile and infectious inflammatory diseases of the central nervous system (CNS) and may lead to the development of neurodegeneration. The present article is designed to highlight the importance of TLRs in the pathogenesis of neuroinflammation under diverse conditions. TLRs are expressed by various immune cells present in CNS along with neurons. However out of thirteen TLRs described in mammals, some are present and active in these cells, while some are absent and are described in detail in main text. The role of various immune cells present in the brain and their role in the pathogenesis of neuroinflammation depending on the type of TLR expressed is described. Thereafter the role of TLRs in bacterial meningitis, viral encephalitis, stroke, Alzheimer's disease (AD), Parkinson's disease (PD), and autoimmune disease including multiple sclerosis (MS) is described. The article is designed for both neuroscientists needing information regarding TLRs in neuroinflammation and TLR biologists or immunologists interested in neuroinflammation.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Several of them, especially TLR2, 4, and 9, have vital contributions to the development of neurodegenerative diseases.276”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [276]
In the citing paper
“TLR activation leads to receptor dimerization and the recruitment of adapter proteins, such as Toll/interleukin 1 receptor (TIR) domain-containing adapter interferon-β (TRIF) and myeloid differentiation primary-response protein 88 (MyD88)276”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [276]
Citations
Cites
Items 201–249 of 249
The immune modulating properties of the heat shock proteins after brain injury
Kim, J. Y., & Yenari, M. A. (2013) · Anatomy & Cell Biology · doi:10.5115/acb.2013.46.1.1 · Cited by 66
Potential Therapeutic Effects of Neurotrophins for Acute and Chronic Neurological Diseases
Cai, J., Hua, F., Yuan, L., Tang, W., Lu, J., Yu, S., Wang, X., & Hu, Y. (2014) · BioMed Research International · doi:10.1155/2014/601084 · Cited by 66
Toll-Like Receptors in Multiple Sclerosis
Racke, M. K., & Drew, P. D. (2009) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-00549-7_9 · Cited by 65
Expression of IL-6 in the ischemic penumbra
Block, F., Peters, M., & Nolden-Koch, M. (2000) · Neuroreport · doi:10.1097/00001756-200004070-00013 · Cited by 63
Long, H., O’Connor, B. P., Zemans, R. L., Zhou, X., Yang, I. V., & Schwartz, D. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093550 · Cited by 62
Hundeshagen, A., Hecker, M., Paap, B. K., Angerstein, C., Kandulski, O., Fatum, C., Hartmann, C., Koczan, D., Thiesen, H., & Zettl, U. K. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-140 · Cited by 61
Eto, A., Muta, T., Yamazaki, S., & Takeshige, K. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)03082-6 · Cited by 60
Medvedev, A. E., Murphy, M., Zhou, H., & Li, X. (2015) · Immunological Reviews · doi:10.1111/imr.12298 · Cited by 60
Lambertsen, K. L., Clausen, B. H., Fenger, C., Wulf, H. C., Owens, T., Dagnæs‐Hansen, F., Meldgaard, M., & Finsen, B. R. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.10.046 · Cited by 60
Ebid, R., Lichtnekert, J., & Anders, H. (2014) · ISRN Nephrology · doi:10.1155/2014/714081 · Cited by 59
Host species-specific usage of the TLR4-LPS receptor complex
Lizundia, R., Sauter, K., Taylor, G., & Werling, D. (2008) · Innate Immunity · doi:10.1177/1753425908095957 · Cited by 59
IκB‐ζ: An Inducible Regulator of Nuclear Factor‐κB
Muta, T. (2006) · Vitamins and hormones · doi:10.1016/s0083-6729(06)74012-2 · Cited by 55
SARM modulates MyD88-mediated TLR activation through BB-loop dependent TIR-TIR interactions
Carlsson, E., Ding, J. L., & Byrne, B. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.11.021 · Cited by 55
T Cells in the Central Nervous System: The Delicate Balance between Viral Clearance and Disease
McGavern, D. B., Homann, D., & Oldstone, M. B. A. (2002) · The Journal of Infectious Diseases · doi:10.1086/344264 · Cited by 52
Interferon‐β inhibits toll‐like receptor 9 processing in multiple sclerosis
Balashov, K. E., Aung, L. L., Vaknin‐Dembinsky, A., Dhib-Jalbut, S. S., & Weiner, H. L. (2010) · Annals of Neurology · doi:10.1002/ana.22136 · Cited by 51
Defining the subcellular sites of innate immune signal transduction
Kagan, J. C. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.06.005 · Cited by 51
Pivotal neuroinflammatory and therapeutic role of high mobility group box 1 in ischemic stroke
Richard, S. A., Sackey, M., Su, Z., & Hua-xi, X. (2017) · Bioscience Reports · doi:10.1042/bsr20171104 · Cited by 51
T cells in the central nervous system: messengers of destruction or purveyors of protection?
Walsh, J. T., Watson, N., & Kipnis, J. (2014) · Immunology · doi:10.1111/imm.12187 · Cited by 51
Amphioxus SARM Involved in Neural Development May Function as a Suppressor of TLR Signaling
Yuan, S., Wu, K., Yang, M., Xu, L., Huang, L., Liu, H., Tao, X., Huang, S., & Xu, A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903675 · Cited by 48
van Well, G. T. J., Sanders, M. S., Ouburg, S., van Furth, A. M., & Morré, S. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035837 · Cited by 45
Derkow, K., Bauer, J. M. J., Hecker, M., Paap, B. K., Thamilarasan, M., Koczan, D., Schott, E., Deuschle, K., Bellmann–Strobl, J., Paul, F., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070626 · Cited by 43
IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury
Thaney, V. E., O’Neill, A. M., Hoefer, M. M., Maung, R., Sánchez, A. B., & Kaul, M. (2017) · Scientific Reports · doi:10.1038/srep46514 · Cited by 43
Toll-Like Receptors in Bacterial Meningitis
Koedel, U. (2009) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-00549-7_2 · Cited by 43
TLR7 Deficiency Leads to TLR8 Compensative Regulation of Immune Response against JEV in Mice
Awais, M., Wang, K., Lin, X., Qian, W., Zhang, N., Wang, C., Wang, K., Zhao, L., Fu, Z. F., & Cui, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00160 · Cited by 42
Neuronal IFN-beta–induced PI3K/Akt-FoxA1 signalling is essential for generation of FoxA1+Treg cells
Liu, Y., Marín, A., Ejlerskov, P., Rasmussen, L. M., Prinz, M., & Issazadeh‐Navikas, S. (2017) · Nature Communications · doi:10.1038/ncomms14709 · Cited by 38
Homeostatic interferon expression in neurons is sufficient for early control of viral infection
Cavanaugh, S. E., Holmgren, A. M., & Rall, G. F. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.12.012 · Cited by 37
Gooshe, M., Abdolghaffari, A. H., Gambuzza, M. E., & Rezaei, N. (2014) · Reviews in the Neurosciences · doi:10.1515/revneuro-2014-0026 · Cited by 36
Review: Therapeutic Targeting of HMGB1 in Stroke
Tian, X., Liu, C., Zhang, S., & Chen, G. (2016) · Current Drug Delivery · doi:10.2174/1567201813666160808111933 · Cited by 35
Muta, T., Yamazaki, S., Eto, A., Motoyama, M., & Takeshige, K. (2003) · Journal of Endotoxin Research · doi:10.1177/09680519030090030801 · Cited by 34
Innate Immunity in Sepsis Pathogenesis and Its Modulation: New Immunomodulatory Targets Revealed
Kumar, V., & Sharma, A. (2008) · Journal of Chemotherapy · doi:10.1179/joc.2008.20.6.672 · Cited by 33
Self-citationAstrocytes Exert and Control Immune Responses in the Brain
Cordiglieri, C., & Farina, C. (2010) · Current Immunology Reviews · doi:10.2174/157339510791823655 · Cited by 31
Kinsella, S. M., König, H., & Prehn, J. H. M. (2016) · eNeuro · doi:10.1523/eneuro.0099-15.2016 · Cited by 30
Kinsella, S. M., Fichtner, M. W., Watters, O., König, H., & Prehn, J. H. M. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1143-3 · Cited by 30
Fadnis, P., Ravi, V., Desai, A. S., Turtle, L. C. W., & Solomon, T. (2013) · Viral Immunology · doi:10.1089/vim.2013.0016 · Cited by 29
Beyond TLR Signaling—The Role of SARM in Antiviral Immune Defense, Apoptosis & Development
Panneerselvam, P., & Ding, J. (2015) · International Reviews of Immunology · doi:10.3109/08830185.2015.1065826 · Cited by 28
Béjot, Y., Osseby, G., Grémeaux, V., Durier, J., Rouaud, O., Moreau, T., & Giroud, M. (2009) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2009.08.062 · Cited by 27
Impaired toll-like receptor 8 signaling in multiple sclerosis
Johnson, T. P., Tyagi, R., Patel, K., Schiess, N., Calabresi, P. A., & Nath, A. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-74 · Cited by 26
McCabe, K., Concannon, R. M., McKernan, D. P., & Dowd, E. (2017) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2017.07.007 · Cited by 25
Kalinderi, K., Bostantjopoulou, S., Katsarou, Z., & Fidani, L. (2012) · Neurological Sciences · doi:10.1007/s10072-012-1106-x · Cited by 22
Gowin, E., Świątek-Kościelna, B., Kałużna, E. M., Nowak, J., Michalak, M., Wysocki, J., & Januszkiewicz‐Lewandowska, D. (2017) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2017.04.024 · Cited by 22
Zhang, H. (2011) · Frontiers in Bioscience-Scholar · doi:10.2741/193 · Cited by 21
Association of TLR9 polymorphisms with sporadic Parkinson's disease in Chinese Han population
Zhu, K., Teng, J., Zhao, J., Liu, H., & Xie, A. (2015) · International Journal of Neuroscience · doi:10.3109/00207454.2015.1050591 · Cited by 19
Zhang, P., Zhang, N., Liu, L., Zheng, K., Zhu, L., Zhu, J., Cao, L., Jiang, Y., Liu, G., & He, Q. (2017) · Scientific Reports · doi:10.1038/srep42796 · Cited by 18
Rodet, F., Tasiemski, A., Boidin‐Wichlacz, C., Camp, C. V., Vuillaume, C., Slomianny, C., & Salzet, M. (2015) · Scientific Reports · doi:10.1038/srep09624 · Cited by 17
Activation of microglial Toll‐like receptor 3 promotes neuronal survival against cerebral ischemia
Jeong, S., Jeon, R., Choi, Y. K., Jung, J. E., Liang, A. C., Xing, C., Wang, X., Lo, E. H., & Song, Y. S. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13441 · Cited by 16
TLR4 and TLR2 activation is differentially associated with age during Parkinson’s disease
Sobrinho, H. M. D. R., da Silva, D. J., Gomides, L. F., Dorta, M. L., de Oliveira, M. A. P., & Ribeiro‐Dias, F. (2017) · Immunological Investigations · doi:10.1080/08820139.2017.1379024 · Cited by 15
Song, X., & Qian, Y. (2013) · Nature Medicine · doi:10.1038/nm.3176 · Cited by 9
Ischemic Stroke Caused by a Hyaluronic Acid Gel Embolism Treated with Tissue Plasminogen Activator
Lee, S., Jung, J., Seo, J., & Kim, E. (2017) · Journal of Neurocritical Care · doi:10.18700/jnc.170020 · Cited by 7
Mukherjee, S., Akbar, I., Kumari, B., Vrati, S., Basu, A., & Banerjee, A. K. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/324715 · Cited by 1
Flagged first, then by citations
6 of the 255 references couldn’t be matched to a known paper.
Research works printed but not linked: 6
- Akira, 2006, TLR signaling, Curr. Top. Microbiol. Immunol., 311, 1
- Kim, 2013, The immune modulating properties of the heat shock proteins after brain injury, Anat. Cell Biol., 46, 1, 10.5115/acb.2013.46.1.1 · DOI
- Landreth, 2009, Article 8. TLRs in Alzheimer's disease, Curr. Top. Microbiol. Immunol., 336, 137
- Okun, 2009, Toll-like receptors in neurodegeneration, Brain Res. Rev., 59, 278, 10.1016/j.brainresrev.2008.09.001 · DOI
- Reed-Geaghan, 2009, CD14 and toll-like receptors 2 and 4 are required for fibrillar A{beta}-stimulated microglial activation, J. Neurosci., 29, 11982, 10.1523/JNEUROSCI.3158-09.2009 · DOI · Paper page
- O. Takeuchi, S. Akira, Pattern recognition receptors and inflammation, Cell 140(6) 805-820. · DOI · Paper page
Cited by
Sorted by citations
Role of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668
“Several of them, especially TLR2, 4, and 9, have vital contributions to the development of neurodegenerative diseases.(276) TLRs can be activated by pathogen-associated molecular patterns (PAMPs) (e.”
BackgroundNeuroinflammation and depression: A review
Troubat, R., Barone, P., Leman, S., Desmidt, T., Cressant, A., Atanasova, B., Brizard, B., El Hage, W., Surget, A., Belzung, C., et al. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14720 · Cited by 1,107
Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke
Alsbrook, D. L., Napoli, M. D., Bhatia, K., Biller, J., Andalib, S., Hinduja, A., Rodrigues, R., Rodriguez, M., Sabbagh, S. Y., Selim, M. H., et al. (2023) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-023-01282-2 · Cited by 573
Microglia: Agents of the CNS Pro-Inflammatory Response
Rodríguez-Gómez, J. A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M. K. R., Herrera, A. J., Espinosa-Oliva, A. M., Joseph, B., Hajji, N., Venero, J. L., & Burguillos, M. A. (2020) · Cells · doi:10.3390/cells9071717 · Cited by 365
The Beneficial Roles of SIRT1 in Neuroinflammation-Related Diseases
Jiao, F., & Gong, Z. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/6782872 · Cited by 294
Metadata
- Authors
- Kumar, V.
- Affiliations
- The University of Queensland (AU)
- Corresponding author
- Kumar, V.
- ORCID
- Kumar, V.
- Venue
- Journal of Neuroimmunology
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 332
- Pages
- 16-30
- ISSN
- 0165-5728 (ISSN-L)
- OpenAlex
- W2924166680
- Cited by
- 331
- References
- 255
- Citations by year
- 2026: 25 · 2025: 41 · 2024: 50 · 2023: 55 · 2022: 61 · 2021: 47 · 2020: 46 · 2019: 6
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroimmunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- Toll-like receptors, neuroinflammation, pattern recognition receptors, damage-associated molecular patterns, NF-κB signaling, inflammatory cytokines, neurodegeneration, bacterial meningitis, viral encephalitis, stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis
- MeSH terms
- Alarmins, Pathogen-Associated Molecular Pattern Molecules, Animals, Astrocytes, Brain, Brain Diseases, Cerebrovascular Disorders, Encephalitis, Humans, Meningitis, Neurons, Oligodendroglia, Neuroimmunomodulation, Signal Transduction, Microglia, Neurodegenerative Diseases, Receptors, Pattern Recognition, Toll-Like Receptors, Myeloid Differentiation Factor 88
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review