Aurintricarboxylic Acid Decreases RNA Toxicity in a Model of Repeat Expansions

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2021 Dec 23

PMID 34941747

Citations 1

Authors

Maya Braun

Shachar Shoshani

Anna Mellul-Shtern

Yuval Tabach

Affiliations

Soon will be listed here.

Abstract

Pathologic expansions of DNA nucleotide tandem repeats may generate toxic RNA that triggers disease phenotypes. RNA toxicity is the hallmark of multiple expansion repeat disorders, including myotonic dystrophy type 1 (DM1). To date, there are no available disease-modifying therapies for DM1. Our aim was to use drug repositioning to ameliorate the phenotype of affected individuals in a nematode model of DM1. As the RNA interference pathway plays a key role in mediating RNA toxicity, we investigated the effect of aurintricarboxylic acid. We demonstrated that by perturbing the RNA interference machinery using aurintricarboxylic acid, we could annihilate the RNA toxicity and ameliorate the phenotype. As our approach targets a universal disease mechanism, it is potentially relevant for more expansion repeat disorders.

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