Accession Number : AD1050126

Title :   RAN Translation as a Therapeutic in ALS

Descriptive Note : Technical Report,01 May 2016,30 Apr 2017

Corporate Author : Leland Standford Junior University Stanford United States

Personal Author(s) : Puglisi, Joseph ; Gitler,Aaron

Full Text :

Report Date : 01 May 2017

Pagination or Media Count : 12

Abstract : Repeat Associated, nonATG (RAN) translation likely plays a key role in ALS disease etiology. Repeat expansionsare common, and lead to translation of toxic repeating peptide products. Our project aims to define themechanisms of RAN translation, and identify inhibitors of the process for therapeutic intervention. Here we reportour results from year 1. We have achieved our stated goals to define in vitro and in vivo systems to screen for RANtranslation. We have shown that RAN translation can be detected in vitro, and demonstrated the role of the 5 capin the process. We have performed in vivo screens that have identified co-factors required for RAN translation, andshowed that a key ribosomal protein, RpS25, is required for RAN translation in patient-derived induced pluripotentstem cells. This result suggests that RAN translation occurs via a non-traditional pathway that can be selectivelyinhibited for treatment. Our results in year 1 provide the platform for screening efforts in year 2.

Descriptors :   CENTRAL NERVOUS SYSTEM DISEASES , inhibitors , therapeutics , detection

Subject Categories : Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE