 Working model of Tau degradation through the Rab35/ESCRT pathway, and its inhibition by glucocorticoids (GC). Rab35 mediates Tau clearance via the endo-lysosomal pathway by recruiting initial ESCRT component Hrs, which recognizes and sorts ubiquitylated Tau into early endosomes for packaging into MVBs. GC suppress transcription of Rab35, which in turn decreases Tau sorting into MVBs and its subsequent degradation by lysosomes, leading to Tau accumulation and related neuronal atrophy. 