Mechanism of action deconvolution of the small-molecule pathological tau aggregation inhibitor Anle138b.

ABSTRACT:

Background

A key histopathological hallmark of Alzheimer's disease (AD) is the presence of neurofibrillary tangles of aggregated microtubule-associated protein tau in neurons. Anle138b is a small molecule which has previously shown efficacy in mice in reducing tau aggregates and rescuing AD disease phenotypes.

Methods

In this work, we employed bioinformatics analysis-including pathway enrichment and causal reasoning-of an in vitro tauopathy model. The model consisted of cultured rat cortical neurons either unseeded or seeded with tau aggregates derived from human AD patients, both of which were treated with Anle138b to generate hypotheses for its mode of action. In parallel, we used a collection of human target prediction models to predict direct targets of Anle138b based on

SUBMITTER: Hosseini-Gerami L 

PROVIDER: S-EPMC10012450 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature