Toll-Like Receptors: Sensor Molecules for Detecting Damage to the Nervous System
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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TLR4 is up-regulated after TBI and recognizes LPSs and endogenous proteins such as high-mobility group box 1 protein, heat shock proteins, and low-density lipoprotein.
“TLR4 is up-regulated after TBI and recognizes LPSs and endogenous proteins, such as high-mobility group box 1 protein, heat shock proteins, and low-density lipoprotein (132).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [132]
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“However, there is no evidence for the in vivo expression of TLR9 in astrocytes for other pathophysiological situations [15].”
BackgroundMaturation, 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].”
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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)…”
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Mechanisms underlying the hyperalgesic responses triggered by joint activation of TLR4
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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).”
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“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].”
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TLR Signaling in Brain Immunity
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Metal ions potentiate microglia responsiveness to endotoxin
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“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
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Expression and Role of Toll-like Receptors in Facial Nerve Regeneration after Facial Nerve Injury
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Cellular and Molecular Responses to Traumatic Brain Injury
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The Influence of Erianin on the Differentiation of Neural Stem Cells into Neurons In Vitro
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“This immune response is characterized by the release of danger signals from neurons and glial cells, activation of resident innate immune cells, recruitment and infiltration of peripheral immune cells, and the secretion of various inflammatory molecules [19] .”
Background
- Authors
- Lee, H., Lee, S., Cho, I.-H., & Joong Lee, S.
- Affiliations
- Seoul National University (KR)
- 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)
- 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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