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Caffeine is an adenosine analog and acts as a nonselective adenosine receptor antagonist. The majority of the effects of caffeine are mainly mediated by the blockade of adenosine receptors, and the proved neuroprotective effects of caffeine in brain disorders have been mimicked by the blockade of adenosine A&lt;sub&gt;2A&lt;\/sub&gt; receptor (A&lt;sub&gt;2A&lt;\/sub&gt;R). A growing body of evidence demonstrates that microglia-mediated neuroinflammation plays a key role in the pathophysiology of brain and retinal diseases. Moreover, the control of microglia reactivity by blocking A&lt;sub&gt;2A&lt;\/sub&gt;R has been proposed to be the mechanism underlying the observed protective effects of caffeine. 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