In fact, there is robust evidence showing that the pharmacological or genetic deletion of adenosine A2A receptors (A2AR) diminishes neurodegeneration and brain dysfunction in animal models of aging (Prediger et al., 2005), PD (Schwarzschild et al., 2006), AD (Canas et al., 2009; Laurent et al., 2014), epilepsy (El Yacoubi et al., 2008, 2009; Cognato et al., 2010), Machado-Joseph's disease (Gonçalves et al., 2013), chronic stress (Batalha et al., 2013) or ADHD (Pires et al., 2009; Pandolfo et al., 2013). Here, ADORA2A is linked to Machado-Joseph disease.