![]() However, A2ARs are primarily localized in the striatum, olfactory tubercle, and the nucleus accumbens. In the brain, A1, A2B, and A3 receptors have widespread distribution, although A2B and A3 receptors have relatively low levels. Although the specific G proteins activated by each adenosine receptor are known, the intracellular effects of their activation are wide ranging and may vary based on cell function and location. Adenosine exerts its action through activation of four G-protein coupled adenosine receptors, A1, A2A, A2B, and A3 receptors. A large body of research in recent years has given us a much better understanding of these receptors and their roles in the brain, although there is still much that is unknown. This review explores the role of the A1R in the brain, including its normal physiological and pathophysiological effects and this emerging role as a neurodegenerative receptor, and how this may affect future studies.Īdenosine is an essential neuromodulatory molecule in the brain, but due to the widespread expression of adenosine receptors and the ubiquitous presence of adenosine, the complex role of adenosine signaling is not yet fully elucidated. ![]() ![]() Although the A1R has been traditionally described as a neuroprotective receptor due to its inhibitory effects, emerging evidence suggest that prolonged A1R activation may promote neurodegeneration. This review explores current novel research into the function of these two receptors in the brain and their role in neurological diseases and neurodegeneration. Of the four adenosine receptors, the A1 receptor (A1R) and A2A receptor (A2AR) are both highly expressed throughout the brain and have been widely studied. Along with these normal physiological processes, adenosine is also involved in neuropathologies such as stroke, epilepsy, and Parkinson’s disease. Through a family of four G protein-coupled adenosine receptors, A1, A2A, A2B, and A3, adenosine exerts neuromodulatory effects throughout the brain, affecting crucial processes such as normal neuronal signaling, astrocytic function, learning and memory, motor function, feeding, control of sleep, and normal aging processes. ![]() Adenosine signaling has been well studied in the brain and plays a complex role in multiple physiological and pathophysiological processes. ![]()
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