scholarly journals The Aryl Hydrocarbon Receptor: A Mediator and Potential Therapeutic Target for Ocular and Non-Ocular Neurodegenerative Diseases

2020 ◽  
Vol 21 (18) ◽  
pp. 6777
Author(s):  
Mayur Choudhary ◽  
Goldis Malek
Keyword(s):  
Neurodegenerative Diseases ◽  
Aryl Hydrocarbon Receptor ◽  
Current Knowledge ◽  
Transcriptional Response ◽  
Cellular Processes ◽  
Aryl Hydrocarbon ◽  
Metabolic Products ◽  
The Central Nervous System ◽  
Health And Disease

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which senses environmental, dietary or metabolic signals to mount a transcriptional response, vital in health and disease. As environmental stimuli and metabolic products have been shown to impact the central nervous system (CNS), a burgeoning area of research has been on the role of the AHR in ocular and non-ocular neurodegenerative diseases. Herein, we summarize our current knowledge, of AHR-controlled cellular processes and their impact on regulating pathobiology of select ocular and neurodegenerative diseases. We catalogue animal models generated to study the role of the AHR in tissue homeostasis and disease pathogenesis. Finally, we discuss the potential of targeting the AHR pathway as a therapeutic strategy, in the context of the maladies of the eye and brain.

scholarly journals Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Fabien Pifferi ◽  
Benoit Laurent ◽  
Mélanie Plourde
Keyword(s):  
Fatty Acids ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Lipid Transport ◽  
Omega 3 ◽  
Blood Brain ◽  
Brain Interface ◽  
The Central Nervous System ◽  
Health And Disease ◽  
The Brain

Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF. In this review, the current knowledge of how lipids cross these barriers to reach the CNS is presented and discussed. Implications of these processes in health and disease, particularly during aging and neurodegenerative diseases, are also addressed. An assessment provided here is that the current knowledge of how lipids cross these barriers in humans is limited, which hence potentially restrains our capacity to intervene in and prevent neurodegenerative diseases.

scholarly journals Toward Understanding the Role of Aryl Hydrocarbon Receptor in the Immune System: Current Progress and Future Trends

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Hamza Hanieh
Keyword(s):  
Immune System ◽  
Aryl Hydrocarbon Receptor ◽  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Physiological Role ◽  
Clinical Practices ◽  
Aryl Hydrocarbon ◽  
Active Research

The immune system is regulated by distinct signaling pathways that control the development and function of the immune cells. Accumulating evidence suggest that ligation of aryl hydrocarbon receptor (Ahr), an environmentally responsive transcription factor, results in multiple cross talks that are capable of modulating these pathways and their downstream responsive genes. Most of the immune cells respond to such modulation, and many inflammatory response-related genes contain multiple xenobiotic-responsive elements (XREs) boxes upstream. Active research efforts have investigated the physiological role of Ahr in inflammation and autoimmunity using different animal models. Recently formed paradigm has shown that activation of Ahr by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3,3′-diindolylmethane (DIM) prompts the differentiation of CD4+Foxp3+regulatory T cells (Tregs) and inhibits T helper (Th)-17 suggesting that Ahr is an innovative therapeutic strategy for autoimmune inflammation. These promising findings generate a basis for future clinical practices in humans. This review addresses the current knowledge on the role of Ahr in different immune cell compartments, with a particular focus on inflammation and autoimmunity.

scholarly journals The Role of Aryl Hydrocarbon Receptor (AhR) in Brain Tumors

2020 ◽  
Vol 21 (8) ◽  
pp. 2863 ◽  
Author(s):  
Maria L. Perepechaeva ◽  
Alevtina Y. Grishanova
Keyword(s):  
Brain Tumors ◽  
Aryl Hydrocarbon Receptor ◽  
Therapeutic Target ◽  
Current Knowledge ◽  
Cell Types ◽  
Pathological Process ◽  
Aryl Hydrocarbon ◽  
Oncogenic Protein ◽  
Different Cell Types

Primary brain tumors, both malignant and benign, are diagnosed in adults at an incidence rate of approximately 23 people per 100 thousand. The role of AhR in carcinogenesis has been a subject of debate, given that this protein may act as either an oncogenic protein or a tumor suppressor in different cell types and contexts. Lately, there is growing evidence that aryl hydrocarbon receptor (AhR) plays an important part in the development of brain tumors. The role of AhR in brain tumors is complicated, depending on the type of tumor, on ligands that activate AhR, and other features of the pathological process. In this review, we summarize current knowledge about AhR in relation to brain tumors and provide an overview of AhR’s potential as a therapeutic target.

scholarly journals The aryl hydrocarbon receptor and the gut–brain axis

2021 ◽  
Author(s):  
Andreia Barroso ◽  
João Vitor Mahler ◽  
Pedro Henrique Fonseca-Castro ◽  
Francisco J. Quintana
Keyword(s):  
Transcription Factor ◽  
Aryl Hydrocarbon Receptor ◽  
Therapeutic Target ◽  
Potential Value ◽  
Aryl Hydrocarbon ◽  
Immune Mediated ◽  
Health And Disease

AbstractThe aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified as the receptor for dioxin. Almost half a century after its discovery, AHR is now recognized as a receptor for multiple physiological ligands, with important roles in health and disease. In this review, we discuss the role of AHR in the gut–brain axis and its potential value as a therapeutic target for immune-mediated diseases.

scholarly journals Targeting the Gut Microbiota to Relieve the Symptoms of Irritable Bowel Syndrome

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1545
Author(s):  
Tomasz Wollny ◽  
Tamara Daniluk ◽  
Ewelina Piktel ◽  
Urszula Wnorowska ◽  
Anna Bukłaha ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gut Microbiota ◽  
Current Knowledge ◽  
World Population ◽  
Functional Disorder ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Irritable Bowel ◽  
Functional Responsiveness

Irritable bowel syndrome (IBS) is a common, chronic, functional disorder with a large impact on world population. Its pathophysiology is not completely revealed; however, it is certain that dysregulation of the bidirectional communications between the central nervous system (CNS) and the gut leads to motility disturbances, visceral hypersensitivity, and altered CNS processing characterized by differences in brain structure, connectivity and functional responsiveness. Emerging evidence suggests that gut microbiota exerts a marked influence on the host during health and disease. Gut microbiome disturbances can be also important for development of IBS symptoms and its modulation efficiently contributes to the therapy. In this work, we review the current knowledge about the IBS therapy, the role of gut microbiota in pathogenesis of IBS, and we discuss that its targeting may have significant impact on the effectiveness of IBS therapy.

scholarly journals The Aryl Hydrocarbon Receptor in Chronic Kidney Disease: Friend or Foe?

2020 ◽  
Vol 8 ◽  
Author(s):  
Yenan Mo ◽  
Zhaoyu Lu ◽  
Lixin Wang ◽  
Chunlan Ji ◽  
Chuan Zou ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Aryl Hydrocarbon Receptor ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Cellular Processes ◽  
Aryl Hydrocarbon

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that promotes cell responses to small molecules derived from the diet, microorganisms, metabolism and pollutants. The AhR signal regulates many basic cellular processes, including cell cycle progression, adhesion, migration, apoptosis and cell proliferation. Many studies have shown that AhR is associated with chronic kidney disease (CKD) and its complications. This article reviews the current knowledge about the role of AhR in CKD, showing that AhR mediates CKD complications, including cardiovascular disease, anemia, bone disorders, cognitive dysfunction and malnutrition, and that it influences drug metabolism in individuals with CKD. AhR enhances the intestinal barrier function to reduce the harmful effects of uremic toxins. Therefore, understanding the complex roles of AhR during CKD is important to be able to target this transcription factor safely and effectively for CKD prevention and treatment.

scholarly journals The role of aryl hydrocarbon receptor (AhR) in carcinogenesis in people with high level of dioxin

2018 ◽  
Vol 15 (1) ◽  
pp. 1-13
Author(s):  
Lê Thị Kim Dung ◽  
Nguyễn Thị Kim Liên ◽  
Nguyễn Huy Hoàng ◽  
Nông Văn Hải
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
In Vivo Models ◽  
Epithelial Barrier Function ◽  
Cellular Processes ◽  
Aryl Hydrocarbon ◽  
High Level ◽  
Nerve System ◽  
High Degree

The Aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor that is best known for mediating the toxicity and tumor promoting properties of the carcinogen, including of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD - dioxin). Numerous studies for harmful effects on human health of dioxin have been studied. The results showed that dioxin had effects on many of tissues and organs of nerve system, immune system, reproductive system leading to birth defects and causing development of cancers. The AhR is also now known to be involved in a variety of cellular processes, such as the cell cycle, epithelial barrier function, cell migration,and immune function. Through the AhR, dioxin influences the major stages of tumorigenesis- initiation, promotion, progression, and metastasis. Studies of aggressive tumors and tumor cell lines have revealed that AhR levels are elevated and can be found constitutively in the nucleus. A high degree of complexity has emerged regarding the role of AhR in cancer, with clear discrepancies between pro- and anti-tumorigenic activities when utilizing cell culture versus in vivo models of malignancy. Furthermore, various classes of AhR ligands and indeed ligands within the same class can differentially modulate AhR to influence tumorigenic outcomes. This leads to the hypothesis that the AhR is chronically activated in tumors, thus facilitating tumor progression. In this article, we review the results of studies in the literature about the role of AhR in carcinogenesis in humans with high level of dioxin. Information of the influence of AhR on the formation and development of tumors will be useful understanding to develop potential therapeutic modulation through AhR activities in tumors and to provide effective treatment for cancer patients.

scholarly journals The aryl hydrocarbon receptor in liver inflammation

2021 ◽  
Author(s):  
Antonella Carambia ◽  
Fenja Amrei Schuran
Keyword(s):  
Liver Disease ◽  
Immune Responses ◽  
Aryl Hydrocarbon Receptor ◽  
Current Knowledge ◽  
Regulatory Factor ◽  
Potential Therapeutic Target ◽  
Adaptive Immune ◽  
Aryl Hydrocarbon ◽  
Healthy Liver

AbstractThe aryl hydrocarbon receptor (AHR) is a ubiquitously expressed ligand-activated transcription factor with multifaceted physiological functions. In the immune system, AHR has been unequivocally identified as a key regulatory factor that can integrate environmental, dietary, or microbial signals into innate and adaptive immune responses. Correspondingly, AHR activity seems to be most important at barrier organs, such as the gut, skin, and lung. The liver is likewise prominently exposed to gut-derived dietary or microbial AHR ligands and, moreover, generates plenty of AHR ligands itself. Yet, surprisingly little is known about the role of AHR in the regulation of hepatic immune responses, which are normally biased towards tolerance, preventing harmful inflammation in response to innocuous stimuli. In this review, we summarize the current knowledge about the role of AHR in hepatic immune responses in the healthy liver as well as in inflammatory liver disease. Moreover, we discuss AHR as a potential therapeutic target in hepatic disorders, including autoimmune liver disease, liver fibrosis, and liver cancer.

scholarly journals Hypoxia, Acidification and Inflammation: Partners in Crime in Parkinson’s Disease Pathogenesis?

Immuno ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 78-90
Author(s):  
Johannes Burtscher ◽  
Grégoire P. Millet
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Cell Types ◽  
Brain Cell ◽  
Special Focus ◽  
Molecular Alterations ◽  
Research Fields

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.

Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon

2021 ◽  
pp. 2100539
Author(s):  
Robert S. Chapkin ◽  
Laurie A. Davidson ◽  
Hyejin Park ◽  
Un‐Ho Jin ◽  
Yang‐Yi Fan ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Aryl Hydrocarbon
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