Adenosine receptors and Huntington's disease.

Adenosine regulates important pathophysiological functions via four distinct adenosine receptor subtypes (A(1), A(2A), A(2B), and A(3)). The A(1) and A(2A) adenosine receptors (A(1)R and A(2A)R) are major targets of caffeine and have been extensively investigated. Huntington's disease (HD) is a dominant neurodegenerative disease caused by an abnormal CAG expansion in the Huntingtin gene. Since the first genetic HD model was created almost two decades ago, tremendous progress regarding the function of the adenosine receptors in HD has been made. Chronic intake of caffeine was recently shown to be positively associated with the disease onset of HD. Moreover, genetic polymorphism of A(2A)R is believed to impact the age of onset. Given the importance of adenosine receptors as drug targets for human diseases, this review highlights the recent findings that delineate the roles of adenosine receptors in HD and discusses their potential for serving as drug targets and/or biomarkers for HD. Adenosine is a purine nucleoside that regulates important physiological functions via four different adenosine receptors (A(1), A(2A), A(2B), and A(3)). These adenosine receptors have seven transmembrane domains and belong to the G protein-coupled receptor family. The functions of the A(1) adenosine receptor (A(1)R) and A(2A) adenosine receptor (A(2A)R) have been investigated relative to HD. In this review, we summarize the recent findings regarding the role of adenosine receptors in HD and discuss the potential application of adenosine receptors as drug targets and biomarkers for HD.