Adenosinergic System and Central Nervous System Disorders

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Background

Adenosine, a nucleoside derived directly from ATP, has neuromodulatory function and is involved in many physiological functions in the CNS and the periphery. Due to brain adenosine production and the wide adenosine receptor distribution in areas such as forebrain, cerebral cortex, spinal cord and hippocampus, adenosine can regulate sleep, anxiety, pain, cognition, memory and other physiological functions.

Adenosine is formed from AMP by the action of the 5-nucleotidase enzyme. Adenosine can also be synthesized from cAMP and can be converted to inosine by the action of adenosine deaminase in the intra- and extracellular space. Intracellular inosine is formed by the breakdown of adenosine by adenosine deaminase (ADA). Adenosine and inosine signaling occurs through its specific receptors (A1, A2A, A2B, and A3), all of which are metabotropic. All of this ATP-derived machinery, commonly referred to as the adenosinergic system, is widely distributed throughout the mammalian organism and predominantly in the central nervous system (CNS). Adenosine and inosine have distinct degrees of affinity to adenosine receptors. Then, according to its concentrations and to which receptors they are bind, these molecules can induce physiological and pharmacological effects very similar or completely different. Therefore, any modulation or change on enzyme activity of this system affect the levels of these nucleosides and the activity of adenosine receptors, opening a big avenue to pharmacological tools and therapeutic opportunities.

Adenosine has neuroprotective properties under certain pathological conditions such as trauma, ischemia, seizure, hemorrhage, epilepsy and neurodegenerative diseases such as Alzheimer´s disease and Parkinson´s disease. These effects seem to involve an enhancement of synaptic adenosine levels, Ca+2 influx blockade, inhibition of glutamate release and vasodilation. For this reason, changes in adenosine levels, in the functionality of its receptors or in the enzymes involved in its synthesis or degradation may induce or facilitate the onset of CNS disorders. In addition, pharmacological interventions targeting the adenosinergic system have produced promising results. For example, the activation of the inhibitory A1R by ligands were shown to exert an antinociceptive effect. Further, the blockade of the A2AR, an excitatory receptor, can reduce chronic stress on brain function and improve memory performance, a potential approach to treat neurodegenerative diseases.

Because of its great importance in modulating central mechanisms at multiple levels and its potential as drug target in the treatment of different CNS disorders, we invite researchers to spread and share their discoveries on the adenosinergic system in this fascinating area. We welcome in vitro, in vivo and pharmacological studies investigating adenosinergic system modulation and changes in CNS disorders. Also, studies that use pharmacological intervention on the adenosinergic system attempting to discover mechanisms, modulate or improve some of these disorders are encouraged. We welcome submissions of original research articles, reviews, case reports, brief research reports and mini-review articles focusing on, but not limited to, the following topics:

• Adenosine release and CNS disorders, such as stroke, dementia, pain, Parkinson disease, Alzheimer disease, depressive disorders, hyperactivity disorders, epilepsy, schizophrenia and others;
• Adenosine receptors activity and expression or modulation and CNS disorders;
• Pharmacological approaches that target adenosine receptors or affect adenosine levels to ameliorate CNS disorders

Keywords: adenosine, adenosine receptor, P1 receptor, adenosine deaminase, central nervous system disorders

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