Cited by 113Neuroinflammation and Neurodegeneration MechanismsImmune Response and InflammationInflammasome and immune disorders

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Toll-Like Receptors: Sensor Molecules for Detecting Damage to the Nervous System

Lee, Hyunkyoung, Lee, Soojin, Cho, Ik-Hyun, Joong Lee, Sung·2013·Current Protein & Peptide Science

DOI 10.2174/1389203711314010006

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Abstract

Toll-like receptors (TLRs) are type I transmembrane signaling molecules that are expressed in cells of the innate immune system. In these cells, TLRs function as pattern recognition receptors (PRR) that recognize specific molecular patterns derived from microorganisms. Upon activation, TLRs trigger a cascade of intracellular signaling pathways in innate immune cells, leading to the induction of inflammatory and innate immune responses, which in turn regulate adaptive immune responses. In the nervous system, different members of the TLR family are expressed on glial cells (astrocytes, microglia, oligodendrocytes, and Schwann cells) and neurons. Recently, increasing evidence has supported the idea that TLRs also recognize endogenous molecules that are released from damaged tissue, thereby regulating inflammatory responses and subsequent tissue repair. These findings imply that TLRs on glial cells may also be involved in the inflammatory response to tissue damage in the nervous system. In this review, we discuss recent studies on TLR expression in the cells of the nervous system and their roles in acute neurological disorders involving tissue damage such as strokes, traumatic spinal cord and brain injuries, and peripheral nerve injuries.

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BackgroundInfluential
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Background
MIF/CD74 axis participates in inflammatory activation of Schwann cells following sciatic nerve injury
Song, H., Zhu, Z., Zhou, Y., et al. (2019) · Journal of Molecular Histology · doi:10.1007/s10735-019-09832-0 · Cited by 23
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“For instance, oligodendrocytes express TLR2 and 3; endothelial cells express TLR2, 4, and 9; and finally, neuronal cells are shown to express TLR2, 3, 4, 8, and 9 [45, 46].”
Intracerebroventricular injection of miR-146a relieves seizures in an immature rat model of lithium-pilocarpine induced status epilepticus
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“TLR4 is an important membrane receptor protein that is widely expressed on the surface of astrocytes, microglia, oligodendrocytes and neurons (Lee et al., 2013).”
Background
Toll-like receptor 7 is overexpressed in the bladder of Hunner-type interstitial cystitis, and its activation in the mouse bladder can induce cystitis and bladder pain
Ichihara, K., Aizawa, N., Akiyama, Y., Kamei, J., Masumori, N., Andersson, K., Homma, Y., & Igawa, Y. (2017) · Pain · doi:10.1097/j.pain.0000000000000947 · Cited by 21
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“SCs also release fac - tors that promote pain and nerve regeneration, such as cytokines and neurotropic factors (De Logu et al., 2019 ; Lee et al., 2013 ; Scheib & Höke, 2013 ; Su et al., 2016 ; Zhang, Liu, et al., 2018 ).”
La neuro-inflammation
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“In visceral pain conditions, microglia have been shown to produce and secrete the cytokines interleukin-1 β (IL-1 β ), tumor necrosis factor-α (TNF-α ), and other pro-inflammatory factors are increased through a myeloid differentiation factor 88 (MyD88)-dependent signaling cascade in the central nervous system includi…”
Influential
Long noncoding RNA (MEG3) in urinal exosomes functions as a biomarker for the diagnosis of Hunner‐type interstitial cystitis (HIC)
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“However, there is no evidence for the in vivo expression of TLR9 in astrocytes for other pathophysiological situations [15].”
Background
Maturation, Morphology, and Function: The Decisive Role of Intestinal Flora on Microglia: A Review
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“The transcription products of almost all Tolllike receptors are expressed in microglia, including TLR19, but not all TLRs are translated into proteins [48].”
Background
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“To date, 13 members of the TLR family have been identified, of which TLR4 is closely linked to atherosclerosis.(12) The aim of the current study was to investigate the relationship between levels of TLR4 in aortic tissue and the severity of atherosclerosis in patients who underwent coronary artery bypass graft (CABG)…”
Background
Defining and Regulating Acute Inflammatory Lesion Formation during the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis
Bolton, C., & Smith, P. (2015) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527314666150716103629 · Cited by 14
Mechanisms underlying the hyperalgesic responses triggered by joint activation of TLR4
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Saturated fatty acids activate the inflammatory signalling pathway in Schwann cells: Implication in sciatic nerve injury
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Pam3CSK4, a TLR2 ligand, induces differentiation of glioblastoma stem cells and confers susceptibility to temozolomide
Megías, J., Martínez, A., San‐Miguel, T., Gil‐Benso, R., Hidalgo, L. M., Albert-Bellver, D., Carratalá, A., Gozalbo, D., López‐Ginés, C., Gil, M. L., et al. (2019) · Investigational New Drugs · doi:10.1007/s10637-019-00788-2 · Cited by 12
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“Other than microbial products, the TLRs recognize endogenous danger-associated molecular patterns (DAMPs) released from injured tissues which regulate inflammatory responses (Lee et al., 2013).”
Background
Neuroprotection by Neurotropin through Crosstalk of Neurotrophic and Innate Immune Receptors in PC12 Cells
Fukuda, Y., Nakajima, K., & Mutoh, T. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186456 · Cited by 9
“TLR4 is one of the PRRs expressed in neuronal cells and microglia [38,39] that can detect and respond to alarmins/DAMPs, thus mediating microglial activation throughout the CNS [40].”
Background
Preconditioning increases brain resistance against acute brain injury via neuroinflammation modulation
Gao, P., Tang, S., Chen, H., Zhou, X., Ou, Y., Shen, R., & He, Y. (2021) · Experimental Neurology · doi:10.1016/j.expneurol.2021.113712 · Cited by 9
Immunoactive drug carriers in cancer therapy
Meng, F., Kwon, S., Wang, J., & Yeo, Y. (2020) · Elsevier eBooks · doi:10.1016/b978-0-08-102983-1.00003-x · Cited by 13
TLR Signaling in Brain Immunity
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Metal ions potentiate microglia responsiveness to endotoxin
Rachmawati, D., Peferoen, L. A. N., Vogel, D. Y. S., Alsalem, I. W. A., Amor, S., Bontkes, H. J., Blomberg, B. M. E. V., Scheper, R. J., & van Hoogstraten, I. M. W. (2015) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2015.12.013 · Cited by 5
“Several studies have elegantly shown that microglia express TLRs 1-9 (Rosenberger et al. 2014; Lehnardt 2010; Jack et al. 2005; Lee et al. 2013).”
Immune-Based Therapies for Traumatic Brain Injury: Insights from Pre-Clinical Studies
Machado, C. A., Silva, A. C. S. E., de Miranda, A. S., Cordeiro, T. M. E., Ferreira, R. N., de Souza, L. C., Teixeira, A. L., & de Miranda, A. S. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190710173234 · Cited by 5
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TLR2 and TLR4 Are Expressed in Epiretinal Membranes: Possible Links with Vitreous Levels of Complement Fragments and DAMP-Related Proteins
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Background
20( R )‐ginsenoside Rg3 Inhibits Neuroinflammation Induced by Cerebral Ischemia/Reperfusion Injury by Regulating the Toll‐Like Receptor 4/Myeloid Differentiation Factor‐88/Nuclear Factor Kappa B Signaling Pathway
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Background

Authors: Lee, H., Lee, S., Cho, I.-H., & Joong Lee, S.
Affiliations: Seoul National University (KR)
ORCID: Lee, Hyunkyoung
Lee, Soojin
Cho, Ik-Hyun
Venue: Current Protein & Peptide Science
Publisher: Bentham Science Publishers Ltd.
Published: 2013-03-01
Volume: 14
Issue: 1
Pages: 33-42
ISSN: 1389-2037 (ISSN-L)
DOI: 10.2174/1389203711314010006
OpenAlex: W2024660851
Cited by: 113
References: 0
Citations by year: 2026: 2 · 2025: 6 · 2024: 3 · 2023: 9 · 2022: 13 · 2021: 4 · 2020: 8 · 2019: 14 · 2018: 8 · 2017: 12 · 2016: 10 · 2015: 13 · 2014: 10 · 2013: 1
FWCI: 6.35
Type: journal article
Language: en
Open access: closed
Locations: Current Protein and Peptide Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Research Foundation of Korea
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, pattern recognition receptors, innate immunity, nervous system damage, glial cells, astrocytes, microglia, oligodendrocytes, Schwann cells, neuroinflammation, tissue repair, stroke, spinal cord injury, traumatic brain injury, peripheral nerve injury
MeSH terms: Animals, Brain Injuries, Humans, Immunity, Innate, Ligands, Neuralgia, Neurons, Spinal Cord Injuries, Signal Transduction, Inflammation Mediators, Stroke, Toll-Like Receptors, Peripheral Nerve Injuries

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Toll-Like Receptors: Sensor Molecules for Detecting Damage to the Nervous System

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