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

6 Scopus citations

Abstract

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
Pages283-301
Number of pages19
DOIs
StatePublished - Jan 1 2018

Publication series

NameAdvances in Neurobiology
Volume20
ISSN (Print)2190-5215

Keywords

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

ASJC Scopus subject areas

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

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  • Cite this

    Lehmkuhl, E. M., & Zarnescu, D. C. (2018). Lost in translation: Evidence for protein synthesis deficits in ALS/FTD and related neurodegenerative diseases. In Advances in Neurobiology (pp. 283-301). (Advances in Neurobiology; Vol. 20). Springer New York LLC. https://doi.org/10.1007/978-3-319-89689-2_11