Asset Details
Do you wish to reserve the book?
Identification of therapeutics that target eEF1A2 and upregulate utrophin A translation in dystrophic muscles
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Identification of therapeutics that target eEF1A2 and upregulate utrophin A translation in dystrophic muscles
Do you wish to request the book?
Identification of therapeutics that target eEF1A2 and upregulate utrophin A translation in dystrophic muscles
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Identification of therapeutics that target eEF1A2 and upregulate utrophin A translation in dystrophic muscles
2020
Overview
Up-regulation of utrophin in muscles represents a promising therapeutic strategy for the treatment of Duchenne Muscular Dystrophy. We previously demonstrated that eEF1A2 associates with the 5’UTR of utrophin A to promote IRES-dependent translation. Here, we examine whether eEF1A2 directly regulates utrophin A expression and identify via an ELISA-based high-throughput screen, FDA-approved drugs that upregulate both eEF1A2 and utrophin A. Our results show that transient overexpression of eEF1A2 in mouse muscles causes an increase in IRES-mediated translation of utrophin A. Through the assessment of our screen, we reveal 7 classes of FDA-approved drugs that increase eEF1A2 and utrophin A protein levels. Treatment of mdx mice with the 2 top leads results in multiple improvements of the dystrophic phenotype. Here, we report that IRES-mediated translation of utrophin A via eEF1A2 is a critical mechanism of regulating utrophin A expression and reveal the potential of repurposed drugs for treating DMD via this pathway.
One potential approach for the treatment of Duchenne muscular dysrophy is to increase expression of the dystrophin homolog utrophin. Here, the authors show that eEF1A2 regulates utrophin expression, and show that 2 FDA-approved drugs upregulate eEIF1A2 and utrophin level in mice, leading to improvement of the dystrophic phenotype.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 49/98
/ 5' Untranslated Regions - genetics
/ 64
/ 64/110
/ 64/60
/ 96/106
/ 96/63
/ Animals
/ Drug Evaluation, Preclinical
/ Drugs
/ Duchenne's muscular dystrophy
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Internal Ribosome Entry Sites - genetics
/ Mice
/ Muscles
/ Muscular Dystrophy, Duchenne - drug therapy
/ Muscular Dystrophy, Duchenne - genetics
/ Peptide Elongation Factor 1 - antagonists & inhibitors
/ Peptide Elongation Factor 1 - genetics
/ Peptide Elongation Factor 1 - metabolism
/ Pravastatin - therapeutic use
/ Protein Biosynthesis - drug effects
/ Protein Biosynthesis - genetics
/ Science
/ Up-Regulation - drug effects
/ Utrophin
