Joint Computational/Cell-Based Approach for Screening Inhibitors of Tau Oligomerization: A Proof-of-Concept Study.

ABSTRACT:

Background

Tau assembly produces soluble oligomers and insoluble neurofibrillary tangles, which are neurotoxic to the brain and associated with Alzheimer's and Parkinson's diseases. Therefore, preventing tau aggregation is a promising therapy for those neurodegenerative disorders.

Objective

The aim of this study was to develop a joint computational/cell-based oligomerization protocol for screening inhibitors of tau assembly.

Methods

Virtual oligomerization inhibition (VOI) experiment using molecular dynamics simulation was performed to screen potential oligomerization inhibitors of PHF6 hexapeptide. Tau seeding assay, which is directly related to the outcome of therapeutic intervention, was carried out to confirm a ligand's ability in inhibiting tau assembly formation

SUBMITTER: Man VH 

PROVIDER: S-EPMC10276768 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature