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

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RNA Metabolism in Neurodegenerative Diseases

Part of the book series: Advances in Neurobiology ((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.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA

    Erik M. Lehmkuhl & Daniela C. Zarnescu

  2. Department of Neuroscience, University of Arizona, Tucson, AZ, USA

    Daniela C. Zarnescu

  3. Department of Neurology, University of Arizona, Tucson, AZ, USA

    Daniela C. Zarnescu

Authors
  1. Erik M. Lehmkuhl
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  2. Daniela C. Zarnescu
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Correspondence to Daniela C. Zarnescu .

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Editors and Affiliations

  1. Department of Neurobiology and Neurology, Dignityhealth St. Joseph’s Hospital, Barrow Neurological Institute, Phoenix, Arizona, USA

    Rita Sattler

  2. Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Christopher J. Donnelly

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Lehmkuhl, E.M., Zarnescu, D.C. (2018). Lost in Translation: Evidence for Protein Synthesis Deficits in ALS/FTD and Related Neurodegenerative Diseases. In: Sattler, R., Donnelly, C. (eds) RNA Metabolism in Neurodegenerative Diseases. Advances in Neurobiology, vol 20. Springer, Cham. https://doi.org/10.1007/978-3-319-89689-2_11

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