Role of pattern recognition receptors and the microbiota in neurological disorders

Keogh, Ciara E.; Rude, Kavi M.; Gareau, Mélanie G.

doi:10.1113/jp279771

Cited by 20 publications

(14 citation statements)

References 97 publications

(159 reference statements)

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“… 373 – 375 Studies have shown that NOD1/NOD2 may be a new target for the treatment of stress-related gut–brain diseases. 376 The gut–brain axis is a biochemical signal of the digestive tract and central nervous system, which affects all events from brain development to the progression of neurological diseases. The hypothalamic–pituitary–adrenal axis (HPA) is one of the main pathways of gut–brain axis signal transmission.…”

Section: Prr-related Diseasesmentioning

confidence: 99%

Pattern recognition receptors in health and diseases

2021

Sig Transduct Target Ther

857

515

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Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize the specific molecular structures on the surface of pathogens, apoptotic host cells, and damaged senescent cells. PRRs bridge nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce nonspecific anti-infection, antitumor, and other immunoprotective effects. Most PRRs in the innate immune system of vertebrates can be classified into the following five types based on protein domain homology: Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), C-type lectin receptors (CLRs), and absent in melanoma-2 (AIM2)-like receptors (ALRs). PRRs are basically composed of ligand recognition domains, intermediate domains, and effector domains. PRRs recognize and bind their respective ligands and recruit adaptor molecules with the same structure through their effector domains, initiating downstream signaling pathways to exert effects. In recent years, the increased researches on the recognition and binding of PRRs and their ligands have greatly promoted the understanding of different PRRs signaling pathways and provided ideas for the treatment of immune-related diseases and even tumors. This review describes in detail the history, the structural characteristics, ligand recognition mechanism, the signaling pathway, the related disease, new drugs in clinical trials and clinical therapy of different types of PRRs, and discusses the significance of the research on pattern recognition mechanism for the treatment of PRR-related diseases.

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Section: Prr-related Diseasesmentioning

confidence: 99%

Pattern recognition receptors in health and diseases

2021

Sig Transduct Target Ther

857

515

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“…The major activators of the immune response in neurodegenerative diseases are danger-associated molecular patterns (DAMPs) originating from the damaged tissue, including aggregated proteins and various molecules originating from damaged or dying neurons [61,62]. These endogenous motifs are recognized by pattern recognition recep-tors (PRRs), which include a wide spectrum of receptors such as Toll-like receptors, the nucleotide-binding oligomerization domain leucine rich repeat-containing receptors and scavenger receptors, among others [6,[63][64][65].…”

Section: Neuroinflammation In Neurodegenerative Diseases: the Role Of Nf-κb Pathwaymentioning

confidence: 99%

Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration

et al. 2021

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Neurodegenerative diseases are one of the leading causes of disability and death worldwide. Intracellular transduction pathways that end in the activation of specific transcription factors are highly implicated in the onset and progression of pathological changes related to neurodegeneration, of which those related to oxidative stress (OS) and neuroinflammation are particularly important. Here, we provide a brief overview of the key concepts related to OS- and neuroinflammation-mediated neuropathological changes in neurodegeneration, together with the role of transcription factors nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB). This review is focused on the transcription factor p53 that coordinates the cellular response to diverse genotoxic stimuli, determining neuronal death or survival. As current pharmacological options in the treatment of neurodegenerative disease are only symptomatic, many research efforts are aimed at uncovering efficient disease-modifying agents. Natural polyphenolic compounds demonstrate powerful anti-oxidative, anti-inflammatory and anti-apoptotic effects, partially acting as modulators of signaling pathways. Herein, we review the current understanding of the therapeutic potential and limitations of flavonols in neuroprotection, with emphasis on their anti-oxidative, anti-inflammatory and anti-apoptotic effects along the Nrf2, NF-κB and p53 pathways. A better understanding of cellular and molecular mechanisms of their action may pave the way toward new treatments.

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“…Mice were randomly assigned to wounded or unwounded groups to avoid bias in study design. Sample size calculation was performed using G∗Power (3.1) based on data collected in our previous behavioral experiments showing impairments, where α = 0.05, power [1-β] = 0.8 ( Keogh et al., 2021a , 2021b ). Two days prior to wounding surgery, all mice were sedated with 3–5% isoflourane and the dorsal surface was shaved, depilated wounded, and bandaged.…”

Section: Methodsmentioning

confidence: 99%

Skin-brain axis signaling mediates behavioral changes after skin wounding

Fregoso

Hadian

Gallegos

et al. 2021

Brain, Behavior, & Immunity - Health

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Patients with chronic wounds often have associated cognitive dysfunction and depression with an as yet unknown mechanism for this association. To address the possible causality of skin wounding inducing these changes, behavior and cognitive functions of female C57BL/6 mice with an excisional skin wound were compared to unwounded animals. At six days post wounding, animals exhibited anxiety-like behaviors, impaired recognition memory, and impaired coping behavior. Wounded animals also had concomitant increased hippocampal expression of Tnfa, the pattern recognition receptor (PRR) Nod2, the glucocorticoid receptors GR/Nr3c1 and Nr3c2. Prefrontal cortex serotonin and dopamine turnover were increased on day six post-wounding. In contrast to the central nervous system (CNS) findings, day six post -wounding serum catecholamines did not differ between wounded and unwounded animals, nor did levels of the stress hormone corticosterone, TNFα, or TGFβ. Serum IL6 levels were, however elevated in the wounded animals. These findings provide evidence of skin-to-brain signaling, mediated either by elevated serum IL6 or a direct neuronal signaling from the periphery to the CNS, independent of systemic mediators. Wounding in the periphery is associated with an altered expression of inflammatory mediators and PRR genes in the hippocampus, which may be responsible for the observed behavioral deficits.

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Role of pattern recognition receptors and the microbiota in neurological disorders

Cited by 20 publications

References 97 publications

Pattern recognition receptors in health and diseases

Pattern recognition receptors in health and diseases

Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration

Skin-brain axis signaling mediates behavioral changes after skin wounding

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