Cited by 425Adenosine and Purinergic SignalingNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

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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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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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