Spermine increases acetylation of tubulins and facilitates autophagic degradation of prion aggregates.

ABSTRACT: Autolysosomal dysfunction and unstable microtubules are hallmarks of chronic neurodegenerative diseases associated with misfolded proteins. Investigation of impaired protein quality control and clearance systems could therefore provide an important avenue for intervention. To investigate this we have used a highly controlled model for protein aggregation, an in vitro prion system. Here we report that prion aggregates traffic via autolysosomes in the cytoplasm. Treatment with the natural polyamine spermine clears aggregates by enhancing autolysosomal flux. We demonstrated this by blocking the formation of mature autophagosomes resulting in accumulation of prion aggregates in the cytoplasm. Further we investigated the mechanism of spermine's mode of action and we demonstrate that spermine in

SUBMITTER: Phadwal K 

PROVIDER: S-EPMC6030104 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature