Adenosine receptors and brain diseases: neuroprotection and neurodegeneration

Gomes, Catarina V.; Kaster, Manuella P.; Tomé, Angelo R.; Agostinho, Paula M.; Cunha, Rodrigo A.

doi:10.1016/j.bbamem.2010.12.001

Cited by 426Adenosine and Purinergic SignalingNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

Adenosine receptors and brain diseases: neuroprotection and neurodegeneration

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Gomes, Catarina V., Kaster, Manuella P., Tomé, Angelo R., Agostinho, Paula M., Cunha, Rodrigo A.·2011·Biochimica et Biophysica Acta (BBA) - Biomembranes

DOI 10.1016/j.bbamem.2010.12.001

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Abstract

Adenosine acts in parallel as a neuromodulator and as a homeostatic modulator in the central nervous system. Its neuromodulatory role relies on a balanced activation of inhibitory A(1) receptors (A1R) and facilitatory A(2A) receptors (A2AR), mostly controlling excitatory glutamatergic synapses: A1R impose a tonic brake on excitatory transmission, whereas A2AR are selectively engaged to promote synaptic plasticity phenomena. This neuromodulatory role of adenosine is strikingly similar to the role of adenosine in the control of brain disorders; thus, A1R mostly act as a hurdle that needs to be overcame to begin neurodegeneration and, accordingly, A1R only effectively control neurodegeneration if activated in the temporal vicinity of brain insults; in contrast, the blockade of A2AR alleviates the long-term burden of brain disorders in different neurodegenerative conditions such as ischemia, epilepsy, Parkinson's or Alzheimer's disease and also seem to afford benefits in some psychiatric conditions. In spite of this qualitative agreement between neuromodulation and neuroprotection by A1R and A2AR, it is still unclear if the role of A1R and A2AR in the control of neuroprotection is mostly due to the control of glutamatergic transmission, or if it is instead due to the different homeostatic roles of these receptors related with the control of metabolism, of neuron-glia communication, of neuroinflammation, of neurogenesis or of the control of action of growth factors. In spite of this current mechanistic uncertainty, it seems evident that targeting adenosine receptors might indeed constitute a novel strategy to control the demise of different neurological and psychiatric disorders.

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Caffeine protects against MPTP‐induced blood‐brain barrier dysfunction in mouse striatum
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CNTF, not other trophic factors, promotes axonal regeneration of axotomized retinal ganglion cells in adult hamsters.
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RESEARCH ARTICLE: Up‐regulation of Adenosine Receptors in the Frontal Cortex in Alzheimer's Disease
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Nucleotide signaling in nervous system development
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Activation of Adenosine A2AReceptor Facilitates Brain-Derived Neurotrophic Factor Modulation of Synaptic Transmission in Hippocampal Slices
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Synaptic dysfunction in Huntington's disease: a new perspective
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Nanoparticle-mediated brain drug delivery: Overcoming blood–brain barrier to treat neurodegenerative diseases
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Pharmacology of Adenosine Receptors: The State of the Art
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Neuron–glia interactions in the pathophysiology of epilepsy
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Adenosine Kinase: Exploitation for Therapeutic Gain
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Squalenoyl adenosine nanoparticles provide neuroprotection after stroke and spinal cord injury
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Activation of microglial cells triggers a release of brain-derived neurotrophic factor (BDNF) inducing their proliferation in an adenosine A2A receptor-dependent manner: A2A receptor blockade prevents BDNF release and proliferation of microglia
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Metabolite profiling for the identification of altered metabolic pathways in Alzheimer's disease
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Past, present and future of A2A adenosine receptor antagonists in the therapy of Parkinson's disease
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Adenosine A2A receptors modulate glutamate uptake in cultured astrocytes and gliosomes
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Guanosine and its role in neuropathologies
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Optogenetic activation of intracellular adenosine A2A receptor signaling in the hippocampus is sufficient to trigger CREB phosphorylation and impair memory
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Chen, J. (2014) · International review of neurobiology · doi:10.1016/b978-0-12-801022-8.00012-x · Cited by 137 · see citing works
Regulation of neuronal communication by G protein‐coupled receptors
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Astrocytic Adenosine A2A Receptors Control the Amyloid-β Peptide-Induced Decrease of Glutamate Uptake
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Adenosine receptor neurobiology: overview
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Pathological overproduction: the bad side of adenosine
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Caffeine Regulates Frontocorticostriatal Dopamine Transporter Density and Improves Attention and Cognitive Deficits in an Animal Model of Attention Deficit Hyperactivity Disorder
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The physiological effects of caffeine on synaptic transmission and plasticity in the mouse hippocampus selectively depend on adenosine A1 and A2A receptors.
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Ultrasensitive and universal fluorescent aptasensor for the detection of biomolecules (ATP, adenosine and thrombin) based on DNA/Ag nanoclusters fluorescence light-up system
Zhu, Y., Hu, X., Shi, S., Gao, R., Huang, H.-L., Zhu, Y., Lv, X., & Yao, T. (2015) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2015.12.015 · Cited by 105 · see citing works
History and Perspectives of A2AAdenosine Receptor Antagonists as Potential Therapeutic Agents
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Guanosine controls inflammatory pathways to afford neuroprotection of hippocampal slices under oxygen and glucose deprivation conditions
Dal-Cim, T. A., Ludka, F. K., Martins, W. C., Reginato, C., Parada, E., Egea, J., López, M. G., & Tasca, C. I. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12324 · Cited by 100 · see citing works
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Huang, Y., Todd, N., & Thathiah, A. (2017) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.02.001 · Cited by 99 · see citing works
Comorbidities in Neurology: Is adenosine the common link?
Boison, D., & Aronica, E. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.04.031 · Cited by 94 · see citing works
The Role of Adenosine Receptors in Psychostimulant Addiction
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Conspecific alarm substance differently alters group behavior of zebrafish populations: Putative involvement of cholinergic and purinergic signaling in anxiety- and fear-like responses
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Cannabis: A Treasure Trove or Pandora's Box?
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Caffeine and adenosine A2A receptor inactivation decrease striatal neuropathology in a lentiviral‐based model of Machado–Joseph disease
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Adenosine A2A receptor regulation of microglia morphological remodeling-gender bias in physiology and in a model of chronic anxiety
Caetano, L. M., Pinheiro, H., Patrício, P., Mateus‐Pinheiro, A., Alves, N. D., Coimbra, B., Baptista, F. I., Henriques, S. N., Cunha, C., Santos, A. R. S., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.173 · Cited by 86 · see citing works
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Simultaneous imaging of multiple neurotransmitters and neuroactive substances in the brain by desorption electrospray ionization mass spectrometry
Shariatgorji, M., Strittmatter, N., Nilsson, A., Källback, P., Alvarsson, A., Zhang, X., Vallianatou, T., Svenningsson, P., Goodwin, R. J. A., & Andrén, P. E. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.05.004 · Cited by 85 · see citing works
Neurodegeneration and Neuroprotection in Glaucoma.
Gauthier, A. C., & Liu, J. (2016) · Europe PMC (PubMed Central) · Cited by 85 · see citing works
Selective A2A receptor antagonist prevents microglia-mediated neuroinflammation and protects retinal ganglion cells from high intraocular pressure–induced transient ischemic injury
Madeira, M. H., Boia, R., Elvas, F., Martins, T., Cunha, R. A., Ambrósio, A. F., & Santiago, A. R. (2016) · Translational Research · doi:10.1016/j.trsl.2015.11.005 · Cited by 83 · see citing works
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Beneficial and detrimental role of adenosine signaling in diseases and therapy
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Blockade of microglial adenosine A2A receptor suppresses elevated pressure‐induced inflammation, oxidative stress, and cell death in retinal cells
Aires, I. D., Boia, R., Rodrigues‐Neves, A. C., Madeira, M. H., Marques, C., Ambrósio, A. F., & Santiago, A. R. (2019) · Glia · doi:10.1002/glia.23579 · Cited by 85 · see citing works
Adenosine A2AR blockade prevents neuroinflammation-induced death of retinal ganglion cells caused by elevated pressure
Madeira, M. H., Elvas, F., Boia, R., Gonçalves, F. Q., Cunha, R. A., Ambrósio, A. F., & Santiago, A. R. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0333-5 · Cited by 83 · see citing works
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Having a Coffee Break: The Impact of Caffeine Consumption on Microglia-Mediated Inflammation in Neurodegenerative Diseases
Madeira, M. H., Boia, R., Ambrósio, A. F., & Santiago, A. R. (2017) · Mediators of Inflammation · doi:10.1155/2017/4761081 · Cited by 84 · see citing works
Levodopa-Induced Dyskinesias in Parkinson’s Disease: An Overview on Pathophysiology, Clinical Manifestations, Therapy Management Strategies and Future Directions
di Biase, L., Pecoraro, P. M., Carbone, S. P., Caminiti, M. L., & Lazzaro, V. D. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12134427 · Cited by 86 · see citing works
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Role of Microglia Adenosine A2AReceptors in Retinal and Brain Neurodegenerative Diseases
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Oncostatin M, an Underestimated Player in the Central Nervous System
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Peripheral Blood Mononuclear Cells as a Laboratory to Study Dementia in the Elderly
Arosio, B., D’Addario, C., Gussago, C., Casati, M., Tedone, E., Ferri, E., Nicolini, P., Rossi, P. D., Maccarrone, M., & Mari, D. (2014) · BioMed Research International · doi:10.1155/2014/169203 · Cited by 73 · see citing works
Treatment of chronic neuropathic pain: purine receptor modulation
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Glial adenosine kinase – A neuropathological marker of the epileptic brain
Aronica, E., Sandau, U. S., Iyer, A. M., & Boison, D. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2013.01.028 · Cited by 70 · see citing works
Purinergic Receptors of the Central Nervous System: Biology, PET Ligands, and Their Applications
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Genetic variation in the adenosine regulatory cycle is associated with posttraumatic epilepsy development
Diamond, M. L., Ritter, A. C., Jackson, E. K., Conley, Y. P., Kochanek, P. M., Boison, D., & Wagner, A. K. (2015) · Epilepsia · doi:10.1111/epi.13044 · Cited by 69 · see citing works
Adenosine Receptors in Cerebral Ischemia
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An Expanded Narrative Review of Neurotransmitters on Alzheimer’s Disease: The Role of Therapeutic Interventions on Neurotransmission
Akyuz, E., Arulsamy, A., Aslan, F. S., Sarisözen, B., Guney, B., Hekimoglu, A., Yilmaz, B. N., Retinasamy, T., & Shaikh, M. F. (2025) · Molecular Neurobiology · doi:10.1007/s12035-024-04333-y · Cited by 69 · see citing works
CXCL16 Orchestrates Adenosine A 3 Receptor and MCP-1/CCL2 Activity to Protect Neurons from Excitotoxic Cell Death in the CNS
Rosito, M., Deflorio, C., Limatola, C., & Trettel, F. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4046-11.2012 · Cited by 68 · see citing works
Understanding the Role of Adenosine A2AR Heteroreceptor Complexes in Neurodegeneration and Neuroinflammation
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Advancements in the Blood–Brain Barrier Penetrating Nanoplatforms for Brain Related Disease Diagnostics and Therapeutic Applications
Thangudu, S., Cheng, F., & Su, C. (2020) · Polymers · doi:10.3390/polym12123055 · Cited by 64 · see citing works
Treatment with A2A receptor antagonist KW6002 and caffeine intake regulate microglia reactivity and protect retina against transient ischemic damage
Boia, R., Elvas, F., Madeira, M. H., Aires, I. D., Rodrigues‐Neves, A. C., Tralhão, P., Szabó, E. C., Baqi, Y., Müller, C. E., Tomé, Â. R., et al. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.451 · Cited by 64 · see citing works
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Purinergic Signaling and Related Biomarkers in Depression
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The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance
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Adenosine Receptors and Neurological Disease: Neuroprotection and Neurodegeneration
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Authors: Gomes, C. V., Kaster, M. P., Tomé, A. R., Agostinho, P. M., & Cunha, R. A.
Affiliations: University of Coimbra (PT)
Corresponding author: Cunha, Rodrigo A.
ORCID: Kaster, Manuella P.
Agostinho, Paula M.
Cunha, Rodrigo A.
Venue: Biochimica et Biophysica Acta (BBA) - Biomembranes
Publisher: Elsevier BV
Published: 2011-05
Volume: 1808
Issue: 5
Pages: 1380-1399
ISSN: 0005-2736 (ISSN-L)
DOI: 10.1016/j.bbamem.2010.12.001
OpenAlex: W2081196843
Cited by: 419
References: 473
Citations by year: 2026: 9 · 2025: 18 · 2024: 15 · 2023: 21 · 2022: 30 · 2021: 24 · 2020: 37 · 2019: 43 · 2018: 36 · 2017: 30 · 2016: 27 · 2015: 38 · 2014: 32 · 2013: 22 · 2012: 26
FWCI: 1.82
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 809 d)
Locations: Biochimica et Biophysica Acta (BBA) - Biomembranes (publishedVersion)
PubMed (publishedVersion)
Funders: Fundação para a Ciência e a Tecnologia
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: adenosine receptors, adenosine A1 receptor, adenosine A2A receptor, neuroprotection, neurodegeneration, neuromodulation, glutamatergic synapses, synaptic plasticity, ischemia, epilepsy, Parkinson's disease, Alzheimer's disease, neuroinflammation, neuron-glia communication, neurogenesis, growth factors, mental illness, adenosine receptor agonists
MeSH terms: Animals, Brain Diseases, Humans, Nerve Degeneration, Receptors, Purinergic P1, Neurotransmitter Agents, Neuroprotective Agents

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Adenosine receptors and brain diseases: neuroprotection and neurodegeneration

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