Toll-Like Receptors (TLRs) and their potential therapeutic applications in diabetic neuropathy

Aghamiri, Seyed Hossein; Komlakh, Khalil; Ghaffari, Mostafa

doi:10.1016/j.intimp.2021.108398

Cited by 14 publications

(15 citation statements)

References 93 publications

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“…TLRs are found in innate immune cells and some non-immune cells. In the CNS these receptors are primarily expressed on microglia and astrocytes, but they can be found also on oligodendrocytes, neurons and Schwann cells [ 37 ]. TLRs recognize a wide array of PAMPs and DAMPs, including, inter alia, bacterial, viral, fungal and protozoan components, heat shock proteins, hyaluronian fragments, ATP or the host’s DNA.…”

Section: Cellular Recognition Of Lpsmentioning

confidence: 99%

“…They can be localized on the surface of the cell (TLR1, 2, 4, 6, 10) or in intracellular compartments (TLR3, 7, 8, 9, 11, 12, 13) [ 36 ]. In brief, TLR-signaling induces recruitment of specific adaptor molecules, leading to activation of the transcription factors, which stimulate production of inflammatory mediators, including cytokines and chemokines, such as TNF-α, IL-1α, IL-1β, IL-6, IL-8, IL-12, IL-23, macrophage inflammatory protein (MIP)-1α, and MIP-1β [ 37 , 38 , 39 ].…”

Section: Cellular Recognition Of Lpsmentioning

confidence: 99%

“…IKKs and MAPKs activate transcription factors: nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), respectively. NF-κB and AP-1 translocate to the nucleus, where they trigger the production of pro-inflammatory mediators, such as IL-6, TNF-α and enzymes, inter alia, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) [ 36 , 37 , 38 ].…”

Section: Cellular Recognition Of Lpsmentioning

confidence: 99%

See 2 more Smart Citations

Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use

2022

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Despite advances in antimicrobial and anti-inflammatory therapies, inflammation and its consequences still remain a significant problem in medicine. Acute inflammatory responses are responsible for directly life-threating conditions such as septic shock; on the other hand, chronic inflammation can cause degeneration of body tissues leading to severe impairment of their function. Neuroinflammation is defined as an inflammatory response in the central nervous system involving microglia, astrocytes, and cytokines including chemokines. It is considered an important cause of neurodegerative diseases, such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Lipopolysaccharide (LPS) is a strong immunogenic particle present in the outer membrane of Gram-negative bacteria. It is a major triggering factor for the inflammatory cascade in response to a Gram-negative bacteria infection. The use of LPS as a strong pro-inflammatory agent is a well-known model of inflammation applied in both in vivo and in vitro studies. This review offers a summary of the pathogenesis associated with LPS exposure, especially in the field of neuroinflammation. Moreover, we analyzed different in vivo LPS models utilized in the area of neuroscience. This paper presents recent knowledge and is focused on new insights in the LPS experimental model.

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Section: Cellular Recognition Of Lpsmentioning

confidence: 99%

Section: Cellular Recognition Of Lpsmentioning

confidence: 99%

Section: Cellular Recognition Of Lpsmentioning

confidence: 99%

See 1 more Smart Citation

Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use

2022

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“…Since death and severe cases of COVID-19 are associated with a hyper-inflammatory response [ 184 ], TLR2 antagonists can be tested for their capacity to alleviate the hyper-inflammatory response in SARS-CoV-2 infection or S protein stimulation. In addition, TLR2 has been demonstrated to be involved in the regulation of immune responses in autoimmune inflammatory diseases [ 185 , 186 ], kidney inflammaging [ 187 ], tissue injuries [ 71 , 188 ], gut microbiome dysbiosis [ 93 , 189 ], diabetes [ 11 ] and cancers [ 190 , 191 , 192 ].…”

Section: Therapeutic Targeting Of Tlr2 Signaling In Diseasesmentioning

confidence: 99%

“…The function of TLRs has been studied extensively in recent decades [ 8 ] ( Figure 1 ). Their capacity as key initiators of innate immune responses makes them attractive therapeutic targets [ 9 , 10 , 11 ]. TLRs are homologs of the Toll gene that was first discovered to be involved in embryonic development in Drosophila [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target

Spaink

2022

Biology

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Innate immunity is considered the first line of defense against microbial invasion, and its dysregulation can increase the susceptibility of hosts to infections by invading pathogens. Host cells rely on pattern recognition receptors (PRRs) to recognize invading pathogens and initiate protective innate immune responses. Toll-like receptor 2 (TLR2) is believed to be among the most important Toll-like receptors for defense against mycobacterial infection. TLR2 has been reported to have very broad functions in infectious diseases and also in other diseases, such as chronic and acute inflammatory diseases, cancers, and even metabolic disorders. However, TLR2 has an unclear dual role in both the activation and suppression of innate immune responses. Moreover, in some studies, the function of TLR2 was shown to be controversial, and therefore its role in several diseases is still inconclusive. Therefore, although TLR2 has been shown to have an important function in innate immunity, its usefulness as a therapeutic target in clinical application is still uncertain. In this literature review, we summarize the knowledge of the functions of TLR2 in host–mycobacterial interactions, discuss controversial results, and suggest possibilities for future research.

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The crosstalk among TLR2, TLR4 and pathogenic pathways; a treasure trove for treatment of diabetic neuropathy

2022

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Toll-Like Receptors (TLRs) and their potential therapeutic applications in diabetic neuropathy

Cited by 14 publications

References 93 publications

Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use

Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use

The Role of TLR2 in Infectious Diseases Caused by Mycobacteria: From Cell Biology to Therapeutic Target

The crosstalk among TLR2, TLR4 and pathogenic pathways; a treasure trove for treatment of diabetic neuropathy

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