A2A Adenosine Receptor Agonists and their Potential Therapeutic Applications. An Update

Guerrero, Ángel

doi:10.2174/0929867325666180313110254

Cited by 54 publications

(59 citation statements)

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“…These observations suggest that recommendations of family practitioners to MCS patients should include drastic reduction or even elimination of caffeine, that has been shown to reduce ADORA2A mRNA expression in a dose-and time-dependent manner [44]. Moreover, the administration of molecules capable of targeting A2AR, such as the non selective 5 -N-ethylcarboxamine (NECA) and the selective CGS-21680 (2-phenethylamino-substituted NECA) and PSB-0777 (2-phenylsulfonate-substituted NECA), already developed and tested in inflammatory disorders and other disease paradigms [25,28], could be regarded as an effective pharmacological approach for patients with severe MCS.…”

Section: Discussionmentioning

confidence: 99%

“…The single nucleotide polymorphism (SNP) rs2298383 of ADORA2A gene, encoding for A2AR, is a functional variant that may affect the rate of gene transcription due to its location within a regulatory sequence of the gene [23,24]. Notably, recent literature data demonstrate that a reduction of A2AR protein amounts increases the rate of inflammation [25].…”

Section: Introductionmentioning

confidence: 99%

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The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity

Cannata¹,

Luca²,

Korkina³

et al. 2020

IJMS

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Systemic inflammation and immune activation are striking features of multiple chemical sensitivity (MCS). The rs2298383 SNP of ADORA2A gene, coding for adenosine receptor type 2A (A2AR), has been involved in aberrant immune activation. Here we aimed to assess the prevalence of this SNP in 279 MCS patients and 238 healthy subjects, and its influence on ADORA2A, IFNG and IL4 transcript amounts in peripheral blood mononuclear cells of randomly selected patients (n = 70) and controls (n = 66) having different ADORA2A genotypes. The ADORA2A rs2298383 TT mutated genotype, significantly more frequent in MCS patients than in controls, was associated with a three-fold increased risk for MCS (O.R. = 2.86; C.I. 95% 1.99-4.12, p < 0.0001), while the CT genotype, highly prevalent among controls, resulted to be protective (O.R. = 0.33; C.I. 95% 0.224-0.475, p < 0.0001). Notably, ADORA2A mRNA levels were significantly lower, while IFNG, but not IL4, mRNA levels were significantly higher in TT MCS patients compared with controls. A significant negative correlation was found between ADORA2A and both IFNG and IL4, while a significant positive correlation was found between IFNG and IL4. These findings suggest that A2AR defective signaling may play a relevant role in PBMC shift towards a pro-inflammatory phenotype in MCS patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity

Cannata¹,

Luca²,

Korkina³

et al. 2020

IJMS

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“…CBD is also an agonist of adenosine A 2A receptors [61], which are G-protein coupled receptors. They are expressed in various cell types, participate in numerous physiological and pathological processes and also regulate inflammatory processes [105]. Adenosine and its agonists exhibit anti-inflammatory activity in vivo [106].…”

Section: Adenosine a 2a Receptorsmentioning

confidence: 99%

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

2019

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Cannabidiol (CBD) is one of the main pharmacologically active phytocannabinoids of Cannabis sativa L. CBD is non-psychoactive but exerts a number of beneficial pharmacological effects, including anti-inflammatory and antioxidant properties. The chemistry and pharmacology of CBD, as well as various molecular targets, including cannabinoid receptors and other components of the endocannabinoid system with which it interacts, have been extensively studied. In addition, preclinical and clinical studies have contributed to our understanding of the therapeutic potential of CBD for many diseases, including diseases associated with oxidative stress. Here, we review the main biological effects of CBD, and its synthetic derivatives, focusing on the cellular, antioxidant, and anti-inflammatory properties of CBD.Antioxidants 2020, 9, 21 2 of 20 Moreover, this phytocannabinoid accelerated wound healing in a diabetic rat model by protecting the endothelial growth factor (VEGF) [11]. In addition, by preventing the formation of oxidative stress in the retina neurons of diabetic animals, CBD counteracted tyrosine nitration, which can lead to glutamate accumulation and neuronal cell death [12].This review summarizes the chemical and biological effects of CBD and its natural and synthetic derivatives. Particular attention was paid to the antioxidant and anti-inflammatory effects of CBD and its derivatives, bearing in mind the possibilities of using this phytocannabinoid to protect against oxidative stress and the consequences associated with oxidative modifications of proteins and lipids. Although CBD demonstrates safety and a good side effect profile in many clinical trials [4], all of the therapeutic options for CBD discussed in this review are limited in a concentration-dependent manner. Molecular Structure of CBDCBD is a terpenophenol compound containing twenty-one carbon atoms, with the formula C 21 H 30 O 2 and a molecular weight of 314.464 g/mol (Figure 1). The chemical structure of cannabidiol, 2-[1R-3-methyl-6R-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1, 3-benzenediol, was determined in 1963 [13]. The current IUPAC preferred terminology is 2-[(1R,6R)-3-methyl-6-prop-1-en-2-ylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol. Naturally occurring CBD has a (−)-CBD structure [14]. The CBD molecule contains a cyclohexene ring (A), a phenolic ring (B) and a pentyl side chain. In addition, the terpenic ring (A) and the aromatic ring (B) are located in planes that are almost perpendicular to each other [15]. There are four known CBD side chain homologs, which are methyl, n-propyl, n-butyl, and n-pentyl [16]. All known CBD forms (Table 1) have absolute trans configuration in positions 1R and 6R [16].

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“…Further studies will be needed to fully validate such a strategy at a preclinical level; however, it should be recalled that available A 2A R agonists suffer from serious drawbacks, including reduced metabolic stability, 54 brain penetration, 55 and serious side-effects such as reduction of blood pressure and slowdown of heart rate. 56 Thus, the development of potent, selective A 2A R…”

Section: Adenosine and Adenosine Receptors In Npc1 Diseasementioning

confidence: 99%

Adenosine and Adenosine A_2AReceptors as Targets for the Treatment of Niemann Pick Type C Disease

FerranteAntonella

VisentinSergio

NuccioChiara

et al. 2019

Journal of Caffeine and Adenosine Research

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Niemann Pick type C (NPC) is a rare neurovisceral disorder characterized by progressive hepatosplenomegaly, neurodegeneration, and premature death; it is caused by mutations in genes coding for two lysosomal proteins: the transmembrane NPC1 and the soluble NPC2. Mutations in both of them cause intracellular accumulation of cholesterol and other lipids in the endo/lysosomal compartment. Currently, an inhibitor of glycosphingolipid synthesis is the only drug approved by the European Medicines Agency, but it only reduces rate of disease progression; for this reason, the search for new druggable targets is urgent. In the present review, the adenosinergic system with a particular focus onto the adenosine A 2A receptor will be presented as a potential therapeutic target for NPC and results obtained in cellular and animal models of the disease will be discussed.

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A2A Adenosine Receptor Agonists and their Potential Therapeutic Applications. An Update

Cited by 54 publications

References 0 publications

The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity

The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

Adenosine and Adenosine A_2AReceptors as Targets for the Treatment of Niemann Pick Type C Disease

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A2A Adenosine Receptor Agonists and their Potential Therapeutic Applications. An Update

Cited by 54 publications

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The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity

The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity

Antioxidative and Anti-Inflammatory Properties of Cannabidiol

Adenosine and Adenosine A2AReceptors as Targets for the Treatment of Niemann Pick Type C Disease

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Adenosine and Adenosine A_2AReceptors as Targets for the Treatment of Niemann Pick Type C Disease