RHEB and Parkinson disease: For example, in PD, acute upregulation of mTOR signaling via constitutively active Akt or Rheb may be beneficial to cell survival and axonal growth but prolonged activation, as with Tsc1 or Pten deletion, is detrimental to DA output (Diaz-Ruiz et al., 2009; Domanskyi et al., 2011; Kosillo et al., 2019; Zhu et al., 2019).