Inhibition of Aβ₄₂ oligomerization in yeast by a PICALM ortholog and certain FDA approved drugs.

ABSTRACT: The formation of small Aβ₄₂ oligomers has been implicated as a toxic species in Alzheimer disease (AD). In strong support of this hypothesis we found that overexpression of Yap1802, the yeast ortholog of the human AD risk factor, phosphatidylinositol binding clathrin assembly protein (PICALM), reduced oligomerization of Aβ₄₂ fused to a reporter in yeast. Thus we used the Aβ₄₂-reporter system to identify drugs that could be developed into therapies that prevent or arrest AD. From a screen of 1,200 FDA approved drugs and drug-like small compounds we identified 7 drugs that reduce Aβ₄₂ oligomerization in yeast: 3 antipsychotics (bromperidol, haloperidol and azaperone), 2 anesthetics (pramoxine HCl and dyclonine HCl), tamoxifen citrate, and minocycli

SUBMITTER: Park SK 

PROVIDER: S-EPMC5349104 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature