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Adenosine Receptors and Neurodegeneration

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Despite the significant disease-related societal burden stemming from brain diseases, the mechanisms involved in the progress of neurodegenerative states are largely unrecognized. Major efforts are required to devise novel tools to delay or attenuate different aspects of neurodegeneration including the ...

Despite the significant disease-related societal burden stemming from brain diseases, the mechanisms involved in the progress of neurodegenerative states are largely unrecognized. Major efforts are required to devise novel tools to delay or attenuate different aspects of neurodegeneration including the synaptic dysfunctions, metabolic imbalance, excitotocixity, or neuroinflammation. The adenosinergic system was initially proposed as a paracrine retaliatory system designed to counteract changes in workload triggered by metabolic stress. However, the neuromodulatory role of adenosine receptors are now increasingly recognized and this system is capable not only of protecting against tissue injury, but also of controlling neuronal excitability, neuroplasticity, inflammation, and different high-order brain functions such as cognitive and emotional behaviors related to disease progression.

Four different subtypes of metabotropic adenosine receptors have already been described, named A1, A2A, A2B and A3 receptors. Initially, adenosine receptors were classified as A1 and A2 receptors based on their opposite ability to modify the levels of cAMP. Later, A2 receptors were further divided into A2A and A2B receptors, based on their low affinity (A2B) and higher affinity (A2A) for adenosine and different adenosine analogues. Finally, the A3 receptors were identified by molecular biology techniques based on their lowest homology across species and notable insensitivity to xanthines. Adenosine receptors are expressed in different cell types within the nervous system, and they emerge as attractive candidates to modulate plastic changes in brain circuits relevant to controlling different aspects of neurodegeneration in pathological processes that accompany conditions such as stroke and seizures, Alzheimer’s disease, Parkinson’s disease, Huntington's disease, diabetic encephalopathy, and a wide range of psychiatric disorders.

The present volume of Frontiers aims at giving the best overview of the role of adenosine receptors during aging and neurological/neurodegenerative conditions, as well as of their potential as therapeutic options.


Keywords: Adenosine receptors, Neurodegeneration, Homeostasis, Plasticity


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