Doxycycline promotes proteasome fitness in the central nervous system.

ABSTRACT: Several studies reported that mitochondrial stress induces cytosolic proteostasis in yeast and C. elegans. Notably, inhibition of mitochondrial translation with doxcycyline decreases the toxicity of β-amyloid aggregates, in a C. elegans. However, how mitochondrial stress activates cytosolic proteostasis remains unclear. Further whether doxycycline has this effect in mammals and in disease relevant tissues also remains unclear. We show here that doxycycline treatment in mice drastically reduces the accumulation of proteins destined for degradation by the proteasome in a CNS region-specific manner. This effect is associated with the activation of the ERα axis of the mitochondrial unfolded protein response (UPR^mt), in both males and females. However, sexually dimorphic mechanisms o

SUBMITTER: Jenkins EC 

PROVIDER: S-EPMC8379233 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature