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Lost in Translation: Evidence for Protein Synthesis Deficits in ALS/FTD and Related Neurodegenerative Diseases

  • Erik M. Lehmkuhl
  • Daniela C. Zarnescu
Chapter
Part of the Advances in Neurobiology book series (NEUROBIOL, volume 20)

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.

Keywords

mRNA Translation Ribosome ALS FTD TDP-43 c9orf72 RNA-binding proteins 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Molecular and Cellular BiologyUniversity of ArizonaTucsonUSA
  2. 2.Department of NeuroscienceUniversity of ArizonaTucsonUSA
  3. 3.Department of NeurologyUniversity of ArizonaTucsonUSA

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