Anti-malaria drug artesunate prevents development of amyloid-β pathology in mice by upregulating PICALM at the blood-brain barrier.

ABSTRACT:

Background

PICALM is one of the most significant susceptibility factors for Alzheimer's disease (AD). In humans and mice, PICALM is highly expressed in brain endothelium. PICALM endothelial levels are reduced in AD brains. PICALM controls several steps in Aβ transcytosis across the blood-brain barrier (BBB). Its loss from brain endothelium in mice diminishes Aβ clearance at the BBB, which worsens Aβ pathology, but is reversible by endothelial PICALM re-expression. Thus, increasing PICALM at the BBB holds potential to slow down development of Aβ pathology.

Methods

To identify a drug that could increase PICALM expression, we screened a library of 2007 FDA-approved drugs in HEK293t cells expressing luciferase driven by a human PICALM promoter, followed by a secondary mRNA scree

SUBMITTER: Kisler K 

PROVIDER: S-EPMC9883925 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature