Liver X Receptor: A novel therapeutic target

Patel, Monal; Oza, NA; Is, Anand; Deshpande, SS; Patel, Chirag H.

doi:10.4103/0250-474x.41445

Cited by 26 publications

(15 citation statements)

References 65 publications

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“…3.1.14 | Liver X receptor agonists Liver X receptors (LXRs) are a group of nuclear receptors involved in maintenance of cholesterol homeostasis but their role in other cellular functions such as immune response that can possibly occur through PPAR agonists and nuclear regulation of NF-κB (Patel et al, 2008). LXR agonists such as TO901317 can enhance locomotor function in animal models of PD by suppressing the phosphorylation of IκB-α and NF-κB in glial cells, culminating in p65 downregulation (Paterniti et al, 2017).…”

Section: Estrogenmentioning

confidence: 99%

Nuclear factor‐kappa B (NF‐κB) in pathophysiology of Parkinson disease: Diverse patterns and mechanisms contributing to neurodegeneration

Dolatshahi

Hameghavandi

Sabahi

et al. 2021

Eur J of Neuroscience

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Parkinson's disease (PD) is the second most common neurodegenerative disease and the most common movement disorder, which causes morbidity and mortality and imposes a large burden (Kowal et al., 2013). Sporadic form of PD occurs more abundantly in aging population and causes symptoms like rigidity, bradykinesia, akinesia, resting tremor, motor imbalance, etc (Davie, 2008). It is characterized by selective degeneration and progressive loss of dopaminergic (DA) neurons in substantia nigra pars compacta (SNpc) which give rise to axonal processes innervating striatum (Surmeier, 2018). A myriad of etiologies contribute to DA neuron loss including inflammation, oxidative stress, autophagy, neurotransmission alterations, metabolic changes, etc. However, the

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Section: Estrogenmentioning

confidence: 99%

Nuclear factor‐kappa B (NF‐κB) in pathophysiology of Parkinson disease: Diverse patterns and mechanisms contributing to neurodegeneration

Dolatshahi

Hameghavandi

Sabahi

et al. 2021

Eur J of Neuroscience

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“…LXR is a member of the nuclear receptor family of transcription factors that is closely related to PPARs [ 77 ]. LXR forms heterodimers with the obligate partner retinoid X receptor (RXR), which is activated by retinoic acid and cholesterol derivatives.…”

Section: Lipid Metabolismmentioning

confidence: 99%

“…LXR forms heterodimers with the obligate partner retinoid X receptor (RXR), which is activated by retinoic acid and cholesterol derivatives. LXR is an important regulator of cholesterol, FA, and glucose homeostasis [ 77 ]. LXR activation increases hepatic triglyceride accumulation and cholesterol metabolism in both humans and mice and initiates bile acid degradation in mice [ 78 ].…”

Section: Lipid Metabolismmentioning

confidence: 99%

Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease

2020

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Obesity is the primary risk factor for the pathogenesis of non-alcoholic fatty liver disease (NAFLD), the worldwide prevalence of which continues to increase dramatically. The liver plays a pivotal role in the maintenance of whole-body lipid and glucose homeostasis. This is mainly mediated by the transcriptional activation of hepatic pathways that promote glucose and lipid production or utilization in response to the nutritional state of the body. However, in the setting of chronic excessive nutrition, the dysregulation of hepatic transcriptional machinery promotes lipid accumulation, inflammation, metabolic stress, and fibrosis, which culminate in NAFLD. In this review, we provide our current understanding of the transcription factors that have been linked to the pathogenesis and progression of NAFLD. Using publicly available transcriptomic data, we outline the altered activity of transcription factors among humans with NAFLD. By expanding this analysis to common experimental mouse models of NAFLD, we outline the relevance of mouse models to the human pathophysiology at the transcriptional level.

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“…Our data identi ed differences in transcription of genes associated with metabolic activity between the lines coinciding with differential colonisation levels at 1 dpi. For example, higher activation in the farnesoid x receptor (FXR)/retinoid x receptor activation was present in line 6 1 but liver x receptor (LXR)/RXR, vitamin D receptor (VDR)/RXR and peroxisome proliferatoractivated receptor (PPARα)/RXR activation was higher in line N. FXR, LXR and PPAR-α are mainly associated with lipid metabolism and in the regulation of triglyceride levels in mammals [41][42][43]. However, between them, FXR, LXR and PPAR-α also have various roles in regulating intestinal in ammation and immunity including effects on macrophage in ammatory activity, reducing the presence of reactive oxygen species (ROS) and maintaining the intestinal barrier [44][45][46][47][48][49], and are considered potential therapeutic targets in the case of mammalian IBD [45,50,51].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of caecal tissue in inbred chicken lines that exhibit heritable differences in resistance to Campylobacter jejuni

Russell

Smith

Bremner

et al. 2021

Preprint

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Background Campylobacter jejuni is the leading cause of bacterial gastroenteritis in humans and the handling or consumption of contaminated poultry meat is a key source of infection. Selective breeding of poultry that exhibit elevated resistance to Campylobacter is an attractive control strategy. Here we studied the global transcriptional response of inbred chicken lines that differ in resistance to C. jejuni colonisation at a key site of bacterial persistence. Results Three-week-old chickens of line 61 and N were inoculated orally with C. jejuni strain M1 and caecal contents and tonsils were sampled at 1 and 5 days post-infection. Caecal colonisation was significantly lower in line 61 compared to line N at 1 day post-infection, but not 5 days post-infection. RNA-Seq analysis of caecal tonsils of both lines revealed a limited response to C. jejuni infection compared to age-matched uninfected controls. In line N at days 1 and 5 post-infection, just 8 and 3 differentially expressed genes (DEGs) were detected (fold-change > 2 and false-discovery rate of < 0.05) relative to uninfected controls, respectively. In the relatively resistant line 61, a broader response to C. jejuni was observed, with 69 DEGs relating to immune regulation, cell signalling and metabolism at 1 day post-infection. However, by day 5 post-infection, no DEGs were detected. By far, the greatest number of DEGs were between uninfected birds of the two lines implying that differential resistance to C. jejuni is intrinsic. Of these genes, several Major Histocompatibility Complex class I-related genes (MHCIA1, MHCBL2 and MHCIY) and antimicrobial peptides (MUC2, AvBD10 and GZMA) were expressed to a greater extent in line N. Two genes within quantitative trait loci associated with C. jejuni colonisation were also more highly expressed in line N (ASIC4 and BZFP2). Quantitative reverse-transcriptase PCR analysis of a subset of transcripts confirmed the RNA-Seq results. Conclusions Our data indicate a limited transcriptional response in the caecal tonsils of inbred chickens to intestinal colonisation by Campylobacter but identify a large number of differentially transcribed genes between lines 61 and N that may underlie variation in heritable resistance to C. jejuni.

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Liver X Receptor: A novel therapeutic target

Cited by 26 publications

References 65 publications

Nuclear factor‐kappa B (NF‐κB) in pathophysiology of Parkinson disease: Diverse patterns and mechanisms contributing to neurodegeneration

Nuclear factor‐kappa B (NF‐κB) in pathophysiology of Parkinson disease: Diverse patterns and mechanisms contributing to neurodegeneration

Transcriptional Regulation in Non-Alcoholic Fatty Liver Disease

Transcriptomic analysis of caecal tissue in inbred chicken lines that exhibit heritable differences in resistance to Campylobacter jejuni

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