The Role of Toll-Like Receptors in Oncotherapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu C
PROVIDER: S-EPMC7848423 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
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Project description:Toll-like receptors (TLRs) are commonly referred to a series of evolutionary conserved receptors which recognize and respond to various microbes and endogenous ligands. Growing evidence has demonstrated that the expression of TLRs in the retina is regulated during retinal ischemic diseases, including ischemia-reperfusion injury, glaucoma, diabetic retinopathy (DR) and retinopathy of prematurity (ROP). TLRs can be expressed in multiple cells in the retina, such as glial cells, retinal pigment epithelium (RPE), as well as photoreceptor cells and endothelium cells. Activation of TLRs in retina could initiate a complex signal transduction cascade, induce the production of inflammatory cytokines and regulate the level of co-stimulatory molecules, which play prominent roles in the pathogenesis of retinal ischemic diseases. In this review, we summarized current studies about the relationship between TLRs and ischemic retinopathy. A greater understanding of the effect of TLRs on ischemic injuries may contribute to the development of specific TLR targeted therapeutic strategies in these conditions.
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Project description:Toll-like receptors (TLRs) are dominant components of the innate immune system. Activated by both pathogen-associated molecular patterns and damage-associated molecular patterns, TLRs underpin the pathology of numerous inflammation related diseases that include not only immune diseases, but also cardiovascular disease (CVD), diabetes, obesity, and cancers. Growing evidence has demonstrated that TLRs are involved in multiple cardiovascular pathophysiologies, such as atherosclerosis and hypertension. Specifically, a trial called the Canakinumab Anti-inflammatory Thrombosis Outcomes Study showed the use of an antibody that neutralizes interleukin-1β, reduces the recurrence of cardiovascular events, demonstrating inflammation as a therapeutic target and also the research value of targeting the TLR system in CVD. In this review, we provide an update of the interplay between TLR signaling, inflammatory mediators, and atherothrombosis, with an aim to identify new therapeutic targets for atherothrombotic CVD.
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Project description:BackgroundParkinson's disease (PD) is the second most prevalent neurodegenerative disorder, characterized by motor and non-motor symptoms, significantly affecting patients' life. Pathologically, PD is associated with the extensive degeneration of dopaminergic neurons in various regions of the central nervous system (CNS), specifically the substantia nigra. This neuronal loss is accompanied by the aggregation of misfolded protein, named α-synuclein.Main textRecent studies detected several clues of neuroinflammation in PD samples using postmortem human PD brains and various PD animal models. Some evidence of neuroinflammation in PD patients included higher levels of proinflammatory cytokines in serum and cerebrospinal fluid (CSF), presence of activated microglia in various brain regions such as substantia nigra, infiltration of peripheral inflammatory cells in affected brain regions, and altered function of cellular immunity like monocytes phagocytosis defects. On the other side, Toll-like receptors (TLRs) are innate immune receptors primarily located on microglia, as well as other immune and non-immune cells, expressing pivotal roles in recognizing exogenous and endogenous stimuli and triggering inflammatory responses. Most studies indicated an increased expression of TLRs in the brain and peripheral blood cells of PD samples. Besides, this upregulation was associated with excessive neuroinflammation followed by neurodegeneration in affected regions. Therefore, evidence proposed that TLR-mediated neuroinflammation might lead to a dopaminergic neural loss in PD patients. In this regard, TLR2, TLR4, and TLR9 have the most prominent roles.ConclusionAlthough the presence of inflammation in acute phases of PD might have protective effects concerning the clearance of α-synuclein and delaying the disease advancement, the chronic activation of TLRs and neuroinflammation might lead to neurodegeneration, resulting in the disease progression. Therefore, this study aimed to review additional evidence of the contribution of TLRs and neuroinflammation to PD pathogenesis, with the hope that TLRs could serve as novel disease-modifying therapeutic targets in PD patients in the future.
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