Polyphenols and Neuroprotection: The Role of Adenosine Receptors

The increase of neurodegenerative disease incidence with aging and the lack of effectiveness in present treatments lead to the exploration of new potential neuroprotective agents found in food. Many of these molecules are polyphenols, which have shown antioxidant properties, among others. Resveratrol (RSV) is a polyphenolic compound naturally found in berries, peanuts, grape skin, and red wine. Different cardioprotective, antitumoral, and neuroprotective actions have been attributed to RSV, although molecular mechanisms involved are not well known. RSV consumption seems to be associated with increased adenosine levels. Adenosine is a purine nucleoside widely distributed in the body which exerts its actions through G protein coupled receptor binding, classified into A1, A2A, A2B, and A3 receptors, with A1 and A2B being mainly expressed in brain. A1 receptors seem to be related to neuroprotection, while A2A to neurodegeneration. A1 and A2A receptors have been involved in neurodegenerative diseases such as Alzheimer's disease (AD), Huntington, Parkinson, and other dementia. In postmortem human brain from AD patients both A1 and A2A receptors are upregulated ever since early asymptomatic stages of AD. RSV has been related to adenosine receptor signaling. Moreover, RSV is able to specifically bind to the orthosteric binding site of adenosine receptors modulating their corresponding transduction pathway. Data summarized in the present review suggest that adenosine receptors can mediate healthy RSV actions and open new possibilities for neuroprotection, even treatment, of neurodegenerative diseases in which adenosine receptors have been involved as AD.