A small-molecule microtubule-stabilizing agent safely reduces Aβ plaque and tau pathology in transgenic mouse models of Alzheimer's disease.

ABSTRACT:

Introduction

Intraneuronal inclusions composed of tau protein are found in Alzheimer's disease (AD) and other tauopathies. Tau normally binds microtubules (MTs), and its disengagement from MTs and misfolding in AD is thought to result in MT abnormalities. We previously identified triazolopyrimidine-containing MT-stabilizing compounds that provided benefit in AD mouse models and herein describe the characterization and efficacy testing of an optimized candidate, CNDR-51997.

Methods

CNDR-51997 underwent pharmacokinetic, pharmacodynamic, safety pharmacology, and mouse tolerability testing. In addition, the compound was examined for efficacy in 5XFAD amyloid beta (Aβ) plaque mice and PS19 tauopathy mice.

Results

CNDR-51997 significantly reduced Aβ plaques in 5XFAD mice an

SUBMITTER: Yao Y 

PROVIDER: S-EPMC11247666 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature