Over the past 1 year to 2 years, more studies from various groups have demonstrated that ACE2 can affect or be affected by other components of the RAS in the central nervous system. An in vitro study from Xiao et al. [32] showed that overexpression of ACE2 in neurons attenuates the Ang II-induced upregulation of AT1R, which could result from inhibition of the well-known feed-forward effect of Ang II on its receptor. In vivo, our group showed that overexpression of ACE2 in the mouse brain not only reduces AT1R expression as previously suggested [30] but also increases Mas and AT2R [33••], whereas blockade of AT1R increases brain ACE2 activity in hypertensive mice [31••]. Using a gene-silencing approach, Lin et al. [12•] reported that downregulation of AT1R mRNA is associated with downregulation of ACE2 mRNA in the mouse brainstem. In addition, downregulated ACE2 is accompanied by upregulation of ACE levels in the brain of a heart failure animal model [34] and in multiple sclerosis patients [35] , indicating a special link between ACE2 and ACE in the brain. These data confirmed and extend previous findings that ACE2 interacts with other RAS components in the brain and strengthens the concept that ACE2 is a significant player in the brain RAS.