A pharmacological chaperone improves memory by reducing Aβ and tau neuropathology in a mouse model with plaques and tangles.

ABSTRACT:

Background

The vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex system, an ubiquitous multiprotein assembly responsible for sorting and trafficking protein cargos out of the endosomes. VPS35 can regulate APP metabolism and Aβ formation, and its levels are reduced in Alzheimer's disease (AD) brains. We and others demonstrated that VPS35 genetic manipulation modulates the phenotype of mouse models of AD. However, the translational value of this observation remains to be investigated.

Methods

Triple transgenic mice were randomized to receive a pharmacological chaperone, which stabilizes the retromer complex, and the effect on their AD-like phenotype assessed.

Results

Compared with controls, treated mice had a significant improvement in lea

SUBMITTER: Li JG 

PROVIDER: S-EPMC6975032 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature