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British Journal of Pharmacology Jul 2017Adenosine is an endogenous ubiquitous purine nucleoside, which is increased by hypoxia, ischaemia and tissue damage and mediates a number of physiopathological effects... (Review)
Review
Adenosine is an endogenous ubiquitous purine nucleoside, which is increased by hypoxia, ischaemia and tissue damage and mediates a number of physiopathological effects by interacting with four GPCRs, identified as A , A , A and A . Physiological and acutely increased adenosine is mostly associated with beneficial effects that include vasodilatation and a decrease in inflammation. In contrast, chronic overproduction of adenosine occurs in important pathological states, where long-lasting increases in the nucleoside levels are responsible for the bad side of adenosine associated with chronic inflammation, fibrosis and organ damage. In this review, we describe and critically discuss the pathological overproduction of adenosine and analyse when, where and how adenosine exerts its detrimental effects throughout the body.
Topics: Adenosine; Animals; Humans; Neurodegenerative Diseases
PubMed: 28252203
DOI: 10.1111/bph.13763 -
Nature Structural & Molecular Biology Feb 2016N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA. Recent discoveries of the locations, functions and mechanisms of m6A have shed...
N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA. Recent discoveries of the locations, functions and mechanisms of m6A have shed light on a new layer of gene regulation at the RNA level, giving rise to the field of m6A epitranscriptomics. In this Perspective, we provide an update on the various effects of mammalian m6A modification, which affects many different stages of the RNA life cycle.
Topics: Adenosine; Animals; Epigenesis, Genetic; Humans; Nucleic Acid Conformation; Protein Biosynthesis; RNA; Transcriptome
PubMed: 26840897
DOI: 10.1038/nsmb.3162 -
Biochimica Et Biophysica Acta. Reviews... Nov 2023As a new pillar of cancer therapy, tumor immunotherapy has brought irreplaceable durable responses in tumors. Considering its low response rate, additional immune... (Review)
Review
As a new pillar of cancer therapy, tumor immunotherapy has brought irreplaceable durable responses in tumors. Considering its low response rate, additional immune regulatory mechanisms will be critical for the development of next-generation immune therapeutics. As a key regulatory mechanism, adenosine (ADO) protects tissues from excessive immune responses, but as a metabolite highly concentrated in tumor microenvironments, extracellular adenosine acts on adenosine receptors (mainly A2A receptors) expressed on MDSCs, Tregs, NK cells, effector T cells, DCs, and macrophages to promote tumor cell escape from immune surveillance by inhibiting the immune response. Amounting preclinical studies have demonstrated the adenosine pathway as a novel checkpoint for immunotherapy. Large number of adenosine pathway targeting clinical trials are now underway, including antibodies against CD39 and CD73 as well as A2A receptor inhibitors. There has been evidence of antitumor efficacy of these inhibitors in early clinical trials among a variety of tumors such as breast cancer, prostate cancer, non-small cell lung cancer, etc. As more clinical trial results are published, the combination of blockade of this pathway with immune checkpoint inhibitors, targeted drugs, traditional chemotherapy medications, radiotherapy and endocrine therapy will provide cancer patients with better clinical outcomes. We would elaborate on the role of CD39-CD73-A2AR pathway in the contribution of tumor microenvironment and the targeting of the adenosinergic pathway for cancer therapy in the review.
Topics: Male; Humans; Adenosine; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immunotherapy; T-Lymphocytes; Tumor Microenvironment
PubMed: 37913941
DOI: 10.1016/j.bbcan.2023.189005 -
Advanced Drug Delivery Reviews 2019Adenosine is a fascinating compound, crucial in many biochemical processes: this ubiquitous nucleoside serves as an essential building block of RNA, is also a component... (Review)
Review
Adenosine is a fascinating compound, crucial in many biochemical processes: this ubiquitous nucleoside serves as an essential building block of RNA, is also a component of ATP and regulates numerous pathophysiological mechanisms via binding to four extracellular receptors. Due to its hydrophilic nature, it belongs to a different world than lipids, and has no affinity for them. Since the 1970's, however, new discoveries have emerged and prompted the scientific community to associate adenosine with the lipid family, especially via liposomal preparations and bioconjugation. This seems to be an arranged marriage, but could it turn into a true love match? This review considered all types of unions established between adenosine and lipids. Even though exciting supramolecular structures were observed with adenosine-lipid conjugates, as well as with liposomal preparations which resulted in promising pre-clinical results, the translation of these technologies to the clinic is still limited.
Topics: Adenosine; Drug Delivery Systems; Humans; Hydrophobic and Hydrophilic Interactions; Lipids; Liposomes
PubMed: 30797954
DOI: 10.1016/j.addr.2019.02.005 -
Biochimica Et Biophysica Acta. Gene... Mar 2019The field of RNA modifications, so-called epitranscriptomics, has flourished over the past years owing to improvements of detection methods and the identification of... (Review)
Review
The field of RNA modifications, so-called epitranscriptomics, has flourished over the past years owing to improvements of detection methods and the identification of important regulatory players. N6-methyladenosine (mA) is the most abundant internal modification in messenger (mRNA) and long non-coding (lncRNA), and controls most steps of RNA metabolism. Its physiological roles range from gametogenesis, stem cell differentiation to immunity, neuronal development and functions, while its alterations are associated with cancer development and progression. In this review we focus on the proteins that catalyze formation of mA (also called writers) on RNA. Interestingly, distinct proteins deposit mA on different classes of RNA, indicating that specific RNA features dictate recognition mechanisms. Associated factors and post-translational modifications can also alter mA enzyme activity. A better understanding of the underlying regulation involved in mA deposition is the first step towards developing tools for cancer therapy and for treatment of other mA-associated diseases.
Topics: Adenosine; Animals; Catalytic Domain; Gene Expression Regulation, Developmental; Humans; Methyltransferases; RNA Processing, Post-Transcriptional; RNA, Messenger
PubMed: 30395944
DOI: 10.1016/j.bbagrm.2018.10.014 -
Ceskoslovenska Fysiologie 2015Adenosine is not just a major component of adenine nucleotides and ribonucleic acids, but also has its own signaling functions. ExtraceIlular level of adenosine in an... (Review)
Review
Adenosine is not just a major component of adenine nucleotides and ribonucleic acids, but also has its own signaling functions. ExtraceIlular level of adenosine in an organism is strictly maintained through the balance between its formation, degradation and transport. Adenosine is formed by enzymatic degradation of adenosine triphosphate and eliminated by phosphorylation to adenosine monophosphate or by deamination to inosine. Transport of adenosine across the cell membrane is ensured by equilibrative and concentrative nucleoside transporters. All these processes participate in maintenance of adenosine level under normal conditions, but a balanced equilibrium can be disrupted in some pathophysiological situations. Extracellular adenosine as a signaling molecule binds to adenosine receptors, which may trigger via their cognate trimeric G proteins different signaling pathways. In this way, adenosine regulates energy homeostasis and affects the function of various organs. Targeted pharmacological manipulations of specific adenosine receptor subtypes or enzymes involved in its metabolism can potentially be used for therapeutic purposes.
Topics: Adenosine; Humans; Nucleoside Transport Proteins; Receptors, Purinergic P1; Signal Transduction
PubMed: 26738245
DOI: No ID Found -
Immunity, Inflammation and Disease Apr 2023Adenosine receptors are P1 class of purinergic receptors that belong to G protein-coupled receptors. There are 4 subtypes of adenosine receptors, namely A1, A2A, A2B,... (Review)
Review
Adenosine receptors are P1 class of purinergic receptors that belong to G protein-coupled receptors. There are 4 subtypes of adenosine receptors, namely A1, A2A, A2B, and A3. A2AR has a high affinity for the ligand adenosine. Under pathological conditions or external stimuli, ATP is sequentially hydrolyzed to adenosine by CD39 and CD73. The combination of adenosine and A2AR can increase the concentration of cAMP and activate a series of downstream signaling pathways, and further playing the role of immunosuppression and promotion of tumor invasion. A2AR is expressed to some extent on various immune cells, where it is abnormally expressed on immune cells in cancers and autoimmune diseases. A2AR expression also correlates with disease progression. Inhibitors and agonists of A2AR may be potential new strategies for treatment of cancers and autoimmune diseases. We herein briefly reviewed the expression and distribution of A2AR, adenosine/A2AR signaling pathway, expression, and potential as a therapeutic target.
Topics: Humans; Receptor, Adenosine A2A; Adenosine; Autoimmune Diseases; Signal Transduction; Neoplasms
PubMed: 37102661
DOI: 10.1002/iid3.826 -
Life Sciences Oct 2021Adenosine, an endogenous purine nucleoside, is a well-known actor of the immune system and the inflammatory response both in physiologic and pathologic conditions. By... (Review)
Review
Adenosine, an endogenous purine nucleoside, is a well-known actor of the immune system and the inflammatory response both in physiologic and pathologic conditions. By acting upon particular, G-protein coupled adenosine receptors, i.e., A1, A2- a & b, and A3 receptors mediate a variety of intracellular and immunomodulatory actions. Several studies have elucidated Adenosine's effect and its up-and downstream molecules and enzymes on the anti-tumor response against several types of cancers. We have also targeted a couple of molecules to manipulate this pathway and get the immune system's desired response in our previous experiences. Besides, the outgrowth of the studies on ocular Adenosine in recent years has significantly enhanced the knowledge about Adenosine and its role in ocular immunology and the inflammatory response of the eye. Glaucoma is the second leading cause of blindness globally, and the recent application of Adenosine and its derivatives has shown the critical role of the adenosine pathway in its pathophysiology. However, despite a very promising background, the phase III clinical trial of Trabodenoson failed to achieve the non-inferiority goals of the study. In this review, we discuss different aspects of the abovementioned pathway in ophthalmology and ocular immunology; following a brief evaluation of the current immunotherapeutic strategies, we try to elucidate the links between cancer immunotherapy and glaucoma in order to introduce novel therapeutic targets for glaucoma.
Topics: Adenosine; Animals; Eye; Glaucoma; Humans; Immunity; Immunotherapy; Neoplasms
PubMed: 34245774
DOI: 10.1016/j.lfs.2021.119796 -
Methods (San Diego, Calif.) Sep 2022Circular RNAs (circRNAs) are a class of noncoding RNAs with covalently single-stranded closed loop structures derived from back-splicing event of linear precursor mRNAs... (Review)
Review
Circular RNAs (circRNAs) are a class of noncoding RNAs with covalently single-stranded closed loop structures derived from back-splicing event of linear precursor mRNAs (pre-mRNAs). N6-methyladenosine (mA), the most abundant epigenetic modification in eukaryotic RNAs, has been shown to play a crucial role in regulating the fate and biological function of circRNAs, and thus affecting various physiological and pathological processes. Accurate identification of mA modification in circRNAs is an essential step to fully elucidate the crosstalk between mA and circRNAs. In recent years, the rapid development of high-throughput sequencing technology and bioinformatic methodology has propelled the establishment of a multitude of approaches to detect circRNAs and mA modification, including in vitro-based and in silico methods. Based on this, the research community has started on a new journey to develop methods for identification of mA modification in circRNAs. In this review, we provide a comprehensive review and evaluation of the existing methods responsible for detecting circRNAs, mA modification, and especially, mA modification in circRNAs, which mainly focused on those developed based on high-throughput technologies and methodology of bioinformatics. This handy reference can help researchers figure out towards which direction this field will go.
Topics: Adenosine; RNA; RNA Splicing; RNA, Circular
PubMed: 35878749
DOI: 10.1016/j.ymeth.2022.07.011 -
Journal of Experimental Botany Sep 2018Throughout all kingdoms of life, ribonucleotides are marked with covalent chemical modifications that change the structure and binding properties of modified RNA... (Review)
Review
Throughout all kingdoms of life, ribonucleotides are marked with covalent chemical modifications that change the structure and binding properties of modified RNA molecules. These marks are deposited by 'writer' proteins, recognized by 'readers', and removed by 'erasers', thus forming an epitranscriptomic system of marks and binding proteins directly analogous to the epigenome. Recent advances in marrying classical biochemical techniques with high-throughput sequencing have enabled detailed mapping of plant epitranscriptomic marks, which in turn yielded insights into how these marks regulate a host of biological processes, from shoot stem cell fate to floral transition and from leaf development to viral activity. In this review, we highlight recent developments in the study of plant epitranscriptomics, with an emphasis on N6-methyladenosine (m6A) and 5-methylcytosine (m5C). These studies have advanced the field beyond descriptive mapping or isolated genetic studies, and produced a more nuanced understanding of how components of the epitranscriptome and their binding proteins directly regulate critical aspects of plant biology.
Topics: 5-Methylcytosine; Adenosine; Plants; Transcriptome
PubMed: 30020491
DOI: 10.1093/jxb/ery262