CRISPR/Cas9-Based Screening of FDA-Approved Drugs for NRF2 Activation: A Novel Approach to Discover Therapeutics for Non-Alcoholic Fatty Liver Disease

نویسندگان

چکیده

With the rising prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now affects 20–25% global population. NAFLD, a progressive condition associated with oxidative stress, can result in cirrhosis and cancer 10% 3% patients suffering respectively. Therapeutic options are currently limited, emphasizing need for novel treatments. In this study, we examined potential activating transcription factor NRF2, crucial player combating as an innovative approach to treating NAFLD. Utilizing CRISPR/Cas9-engineered human HEK293T cell line, were able monitor expression heme oxygenase-1 (HMOX1), NRF2 target, using Nanoluc luciferase tag. Our model was validated known activator, after which screened 1200 FDA-approved drugs, unearthing six compounds (Disulfiram, Thiostrepton, Auranofin, Thimerosal, Halofantrine, Vorinostat) that enhanced activity antioxidant response. These demonstrated protective effects against stress induced by hydrogen peroxide lipid droplets accumulation vitro hepatoma HUH-7 cells. study underscores utility CRISPR/Cas9 tagging identifying activators, paving way NAFLD therapeutics.

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ژورنال

عنوان ژورنال: Antioxidants

سال: 2023

ISSN: ['2076-3921']

DOI: https://doi.org/10.3390/antiox12071363