05-717

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Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition.

Yasin B Seven et al.

Experimental neurology, 323, 113067-113067 (2019-10-21)

Respiratory motor neuron survival is critical for maintenance of adequate ventilation and airway clearance, preventing dependence to mechanical ventilation and respiratory tract infections. Phrenic motor neurons are highly vulnerable in rodent models of motor neuron disease versus accessory inspiratory motor

Systematic comparison of gene expression between murine memory and naive B cells demonstrates that memory B cells have unique signaling capabilities.

Mary M Tomayko et al.

Journal of immunology (Baltimore, Md. : 1950), 181(1), 27-38 (2008-06-21)

Memory B cells play essential roles in the maintenance of long-term immunity and may be important in the pathogenesis of autoimmune disease, but how these cells are distinguished from their naive precursors is poorly understood. To address this, it would

Detection of higher-order G protein-coupled receptor oligomers by a combined BRET-BiFC technique.

Jorge Gandia et al.

FEBS letters, 582(20), 2979-2984 (2008-08-05)

Despite some caveats, G protein-coupled receptor oligomerization is a phenomenon that is becoming largely accepted. Within these oligomers, however, stoichiometry remains to be elucidated. Here, by using bimolecular fluorescence complementation, we visualized adenosine A(2A) receptor homodimers in living cells, showing

Impairment of adenosinergic system in Rett syndrome: Novel therapeutic target to boost BDNF signalling.

Catarina Miranda-Lourenço et al.

Neurobiology of disease, 145, 105043-105043 (2020-08-18)

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant

Blockade of Adenosine A2A Receptor Protects Photoreceptors after Retinal Detachment by Inhibiting Inflammation and Oxidative Stress.

Sha Gao et al.

Oxidative medicine and cellular longevity, 2020, 7649080-7649080 (2020-07-28)

Adenosine A2A receptor (A2AR) signaling is neuroprotective in some retinal damage models, but its role in neuronal survival during retinal detachment (RD) is unclear. We tested the hypothesis that A2AR antagonist ZM241385 would prevent photoreceptor apoptosis by inhibiting retinal inflammation

Endothelial adenosine A2a receptor-mediated glycolysis is essential for pathological retinal angiogenesis.

Zhiping Liu et al.

Nature communications, 8(1), 584-584 (2017-09-21)

Adenosine/adenosine receptor-mediated signaling has been implicated in the development of various ischemic diseases, including ischemic retinopathies. Here, we show that the adenosine A2a receptor (ADORA2A) promotes hypoxia-inducible transcription factor-1 (HIF-1)-dependent endothelial cell glycolysis, which is crucial for pathological angiogenesis in

Evidence for limited D1 and D2 receptor coexpression and colocalization within the dorsal striatum of the neonatal mouse.

Dominik K Biezonski et al.

The Journal of comparative neurology, 523(8), 1175-1189 (2015-01-06)

The striatum is the major input nucleus of the basal ganglia involved in reward processing, goal-directed behaviors, habit learning, and motor control. The striatum projects to the basal ganglia output nuclei via the "direct" and "indirect" pathways, which can be

Adenosine A(2A) receptor up-regulates retinal wave frequency via starburst amacrine cells in the developing rat retina.

Pin-Chien Huang et al.

PloS one, 9(4), e95090-e95090 (2014-04-30)

Developing retinas display retinal waves, the patterned spontaneous activity essential for circuit refinement. During the first postnatal week in rodents, retinal waves are mediated by synaptic transmission between starburst amacrine cells (SACs) and retinal ganglion cells (RGCs). The neuromodulator adenosine

Mariana Temido-Ferreira et al.

Molecular psychiatry, 25(8), 1876-1900 (2018-06-29)

Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this

Forebrain adenosine A2A receptors contribute to L-3,4-dihydroxyphenylalanine-induced dyskinesia in hemiparkinsonian mice.

Xiao, D; Bastia, E; Xu, YH; Benn, CL; Cha, JH; Peterson, TS; Chen, JF; Schwarzschild, MA

The Journal of Neuroscience null

Adenosine A2A receptor stimulation restores cell functions and differentiation in Niemann-Pick type C-like oligodendrocytes.

Chiara De Nuccio et al.

Scientific reports, 9(1), 9782-9782 (2019-07-07)

Niemann Pick type C (NPC) disease is a rare neurovisceral disorder. Mutations in npc1 gene induce an intracellular accumulation of unesterified cholesterol in the endosomal/lysosomal system causing cell death. We recently showed that stimulation of adenosine A2A receptors (A2AR) restores

Changes in adenosine receptors and neurotrophic factors in the SOD1G93A mouse model of amyotrophic lateral sclerosis: Modulation by chronic caffeine.

Nádia Rei et al.

PloS one, 17(12), e0272104-e0272104 (2022-12-15)

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of corticospinal tract motor neurons. Previous studies showed that adenosine-mediated neuromodulation is disturbed in ALS and that vascular endothelial growth factor (VEGF) has a neuroprotective function in ALS mouse models.

Metabotropic glutamate type 5, dopamine D2 and adenosine A2a receptors form higher-order oligomers in living cells.

Nuria Cabello et al.

Journal of neurochemistry, 109(5), 1497-1507 (2009-04-07)

G protein-coupled receptors are known to form homo- and heteromers at the plasma membrane, but the stoichiometry of these receptor oligomers are relatively unknown. Here, by using bimolecular fluorescence complementation, we visualized for the first time the occurrence of heterodimers

Molecular Evidence of Adenosine Deaminase Linking Adenosine A2A Receptor and CD26 Proteins.

Estefanía Moreno et al.

Frontiers in pharmacology, 9, 106-106 (2018-03-03)

Adenosine is an endogenous purine nucleoside that acts in all living systems as a homeostatic network regulator through many pathways, which are adenosine receptor (AR)-dependent and -independent. From a metabolic point of view, adenosine deaminase (ADA) is an essential protein

The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function.

Vânia L Batalha et al.

Scientific reports, 6, 31493-31493 (2016-08-12)

Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A2A receptor (A2AR), which is upregulated in the human forebrain of aged and Alzheimer's disease (AD) patients. We have previously shown that an anti-A2AR therapy reverts

An Anti-Parkinson's Disease Drug via Targeting Adenosine A2A Receptor Enhances Amyloid-β Generation and γ-Secretase Activity.

Jing Lu et al.

PloS one, 11(11), e0166415-e0166415 (2016-11-12)

γ-secretase mediates the intramembranous proteolysis of amyloid precursor protein (APP) and determines the generation of Aβ which is associated with Alzheimer's disease (AD). Here we identified that an anti-Parkinson's disease drug, Istradefylline, could enhance Aβ generation in various cell lines

Istradefylline reduces memory deficits in aging mice with amyloid pathology.

Anna G Orr et al.

Neurobiology of disease, 110, 29-36 (2017-11-05)

Adenosine A2A receptors are putative therapeutic targets for neurological disorders. The adenosine A2A receptor antagonist istradefylline is approved in Japan for Parkinson's disease and is being tested in clinical trials for this condition elsewhere. A2A receptors on neurons and astrocytes

Detecting G protein-coupled receptor complexes in postmortem human brain with proximity ligation assay and a Bayesian classifier.

Ying Zhu et al.

BioTechniques, 68(3), 122-129 (2019-12-21)

Despite the controversy regarding the existence and physiological relevance of class A G protein-coupled receptor dimerization, there is substantial evidence for functional interactions between the dopamine D2 receptor (D2R) and the adenosine A2A receptor (A2AR). A2AR-D2R complexes have been detected in

Newly synthesized cAMP is integrated at a membrane protein complex signalosome to ensure receptor response specificity.

Raquel Guinzberg et al.

The FEBS journal, 284(2), 258-276 (2016-11-20)

Spatiotemporal regulation of cAMP within the cell is required to achieve receptor-specific responses. The mechanism through which the cell selects a specific response to newly synthesized cAMP is not fully understood. In hepatocyte plasma membranes, we identified two functional and

Expression of the Adenosine A2A-A3 Receptor Heteromer in Different Brain Regions and Marked Upregulation in the Microglia of the Transgenic APPSw,Ind Alzheimer's Disease Model.

Alejandro Lillo et al.

Biomedicines, 10(2) (2022-02-26)

Adenosine (Ado) receptors have been instrumental in the detection of heteromers and other higher-order receptor structures, mainly via interactions with other cell surface G-protein-coupled receptors. Apart from the first report of the A1 Ado receptor interacting with the A2A Ado

Exercise-Induced Adaptations to the Mouse Striatal Adenosine System.

Ella E Bauer et al.

Neural plasticity, 2020, 5859098-5859098 (2020-05-14)

Adenosine acts as a key regulator of striatum activity, in part, through the antagonistic modulation of dopamine activity. Exercise can increase adenosine activity in the brain, which may impair dopaminergic functions in the striatum. Therefore, long-term repeated bouts of exercise

Striatal adenosine A2A and cannabinoid CB1 receptors form functional heteromeric complexes that mediate the motor effects of cannabinoids.

Carriba, P; Ortiz, O; Patkar, K; Justinova, Z; Stroik, J; Themann, A; Muller, C; Woods et al.

Neuropsychopharmacology null

Immunohistochemical localization of adenosine A2A receptors in the rat central nervous system

Rosin, D. L., et al

The Journal of Comparative Neurology, 401, 163-186 (1998)

Detection of G Protein-Coupled Receptor Complexes in Postmortem Human Brain by Proximity Ligation Assay.

Ying Zhu et al.

Current protocols in neuroscience, 91(1), e86-e86 (2020-01-17)

Combining immunological and molecular biological methods, the antibody-based proximity ligation assay (PLA) has been used for more than a decade to detect and quantify protein-protein interactions, protein modification, and protein expression in situ, including in brain tissue. However, the transfer

Hippocampal synaptic dysfunction in the SOD1G93A mouse model of Amyotrophic Lateral Sclerosis: Reversal by adenosine A2AR blockade.

N Rei et al.

Neuropharmacology, 171, 108106-108106 (2020-04-21)

Amyotrophic Lateral Sclerosis (ALS) mostly affects motor neurons, but non-motor neural and cognitive alterations have been reported in ALS mouse models and patients. Here, we evaluated if time-dependent biphasic changes in synaptic transmission and plasticity occur in hippocampal synapses of

Homo-oligomerization of the human adenosine A2A receptor is driven by the intrinsically disordered C-terminus.

Khanh Dinh Quoc Nguyen et al.

eLife, 10 (2021-07-17)

G protein-coupled receptors (GPCRs) have long been shown to exist as oligomers with functional properties distinct from those of the monomeric counterparts, but the driving factors of oligomerization remain relatively unexplored. Herein, we focus on the human adenosine A2A receptor

Allosteric interactions between agonists and antagonists within the adenosine A2A receptor-dopamine D2 receptor heterotetramer.

Jordi Bonaventura et al.

Proceedings of the National Academy of Sciences of the United States of America, 112(27), E3609-E3618 (2015-06-24)

Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which

Ultrastructural localization of adenosine A2A receptors suggests multiple cellular sites for modulation of GABAergic neurons in rat striatum.

Hettinger, B D, et al.

The Journal of Comparative Neurology, 431, 331-346 (2001)

Patterns of A2A extracellular adenosine receptor expression in different functional subsets of human peripheral T cells. Flow cytometry studies with anti-A2A receptor monoclonal antibodies.

M Koshiba et al.

Molecular pharmacology, 55(3), 614-624 (1999-03-03)

Signaling through A2A adenosine receptors (A2AR) regulates T lymphocyte expansion and modulates T cell receptor (TCR)-mediated effector functions in vitro. To understand the role of A2ARs in the regulation of immune response, we investigated the expression levels of this receptor

Overexpression of Adenosine A2A Receptors in Rats: Effects on Depression, Locomotion, and Anxiety.

Coelho, JE; Alves, P; Canas, PM; Valadas, JS; Shmidt, T; Batalha, VL; Ferreira et al.

Frontiers in Psychiatry null

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