RAN Translation as a Therapeutic in ALS

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.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2017
Accession Number
AD1050126

Entities

People

  • Aaron Gitler
  • Joseph Puglisi

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Cell Line
  • Cells
  • Central Nervous System
  • Fungi
  • Gel Electrophoresis
  • Genetic Code
  • Genetics
  • High Temperature
  • Inhibitors
  • Molecules
  • Nervous System
  • Nucleic Acids
  • Physical Properties
  • Platforms
  • Polymers
  • Proteins
  • Stem Cells

Fields of Study

  • Medicine

Readers

  • Clinical Trial Research.
  • Molecular Genetics
  • Molecular and genetic basis of cancer.