Chapter Ten - Adenosine Receptors and Huntington's Disease

Abstract

Adenosine regulates important pathophysiological functions via four distinct adenosine receptor subtypes (A1, A2A, A2B, and A3). The A1 and A2A adenosine receptors (A1R and A2AR) 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 A2AR 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 (A1, A2A, A2B, and A3). These adenosine receptors have seven transmembrane domains and belong to the G protein-coupled receptor family. The functions of the A1 adenosine receptor (A1R) and A2A adenosine receptor (A2AR) 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.