Adenosine: An Endogenous Regulator of the Brain Immune System
Adenosine receptors are major targets of caffeine, the most commonly consumed drug in the world. There is growing evidence that they could also be promising therapeutic targets in a wide variety of conditions including Parkinson's disease, stroke, and Alz
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Adenosine: An Endogenous Regulator of the Brain Immune System
G. Hasko´ . E. S. Vizi
1 Adenosine in Regulating Brain Function in Health and Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 2 Metabolism of Adenosine in the Central Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285 3 Modulation of Astrocyte Function by Adenosine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 286 4 Adenosine Regulates the Function of Resident Microglia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 5 Regulation of Inflammation in the Brain by Adenosine Receptors on Infiltrating Immune Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287 6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
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2008 Springer ScienceþBusiness Media, LLC.
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Adenosine: An endogenous regulator of the brain immune system
Abstract: Adenosine receptors are major targets of caffeine, the most commonly consumed drug in the world. There is growing evidence that they could also be promising therapeutic targets in a wide variety of conditions including Parkinson’s disease, stroke, and Alzheimer’s disease. The immune system of the brain that comprises astrocytes, microglia, and infiltrating immune cells is normally quiescent, but it becomes activated following pathophysiological events, such as ischemia, trauma, inflammation, or infection. Adenosine is an endogenous purine nucleoside that is liberated into the extracellular milieu at sites that encounter these ‘‘stressful’’ stimuli. There are four known subtypes of adenosine receptors (A1, A2A, A2B, and A3) and these receptors are expressed on cells of the brain immune system. Adenosine receptor activation on immune‐competent cells in the brain has both protective actions and injurious consequences. A more thorough understanding of adenosine receptor function in the brain immune system will bring the goal of therapeutic application of adenosine receptor modulators considerably closer. List of Abbreviations: CCL2, C‐C motif ligand 2; C/EBPb, CCAAT/enhancer binding protein b; GFAP, glial fibrillary acidic protein; IL, interleukin; MAPK, mitogen‐activated protein kinase; NF‐kB, nuclear factor‐kB; NTDPase, nucleoside triphosphate diphosphorylase; PLC, phospholipase C; PTG, protein targeting to glycogen; TNF‐a, tumor necrosis factor‐a
1 Adenosine in Regulating Brain Function in Health and Disease Extracellular adenosine is a local modulator with a generally cytoprotective function in the body. One of the most widely recognized effects of adenosine is its ability to control, both under physiological and pathophysiological conditions, central nervous system functions. Adenosine binds to one or more of
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