Aβ inhibits SREBP-2 activation through Akt inhibition.

ABSTRACT: We previously demonstrated that oligomeric amyloid β₄₂ (oAβ₄₂) inhibits the mevalonate pathway impairing cholesterol synthesis and protein prenylation. Enzymes of the mevalonate pathway are regulated by the transcription factor SREBP-2. Here, we show that in several neuronal types challenged with oAβ₄₂, SREBP-2 activation is reduced. Moreover, SREBP-2 activation is also decreased in the brain cortex of the Alzheimer's disease (AD) mouse model, TgCRND8, suggesting that SREBP-2 may be affected in vivo early in the disease. We demonstrate that oAβ₄₂ does not affect enzymatic cleavage of SREBP-2 per se, but may impair SREBP-2 transport from the endoplasmic reticulum (ER) to the Golgi. Trafficking of SREBP-2 from the ER to the Golgi requires protein k

SUBMITTER: Mohamed A 

PROVIDER: S-EPMC5748492 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature