Lost in translation: Evidence for protein synthesis deficits in ALS/FTD and related neurodegenerative diseases

Erik M. Lehmkuhl, Daniela C. Zarnescu

Research output: Chapter in Book/Report/Conference proceedingChapter

32 Scopus citations


Cells utilize a complex network of proteins to regulate translation, involving post-transcriptional processing of RNA and assembly of the ribosomal unit. Although the complexity provides robust regulation of proteostasis, it also offers several opportunities for translational dysregulation, as has been observed in many neurodegenerative disorders. Defective mRNA localization, mRNA sequatration, inhibited ribogenesis, mutant tRNA synthetases, and translation of hexanucleotide expansions have all been associated with neurodegenerative disease. Here, we review dysregulation of translation in the context of age-related neurodegeneration and discuss novel methods to interrogate translation. This review primarily focuses on amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a spectrum disorder heavily associated with RNA metabolism, while also analyzing translational inhibition in the context of related neurodegenerative disorders such as Alzheimer’s disease and Huntington’s disease and the translation-related pathomechanisms common in neurodegenerative disease.

Original languageEnglish (US)
Title of host publicationAdvances in Neurobiology
PublisherSpringer New York LLC
Number of pages19
StatePublished - 2018

Publication series

NameAdvances in Neurobiology
ISSN (Print)2190-5215


  • ALS
  • C9orf72
  • FTD
  • MRNA
  • RNA-binding proteins
  • Ribosome
  • TDP-43
  • Translation

ASJC Scopus subject areas

  • Biochemistry
  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience


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