TY - CHAP
T1 - Lost in translation
T2 - Evidence for protein synthesis deficits in ALS/FTD and related neurodegenerative diseases
AU - Lehmkuhl, Erik M.
AU - Zarnescu, Daniela C.
N1 - Publisher Copyright:
© Springer International Publishing AG, part of Springer Nature 2018.
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85048960133&partnerID=8YFLogxK
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U2 - 10.1007/978-3-319-89689-2_11
DO - 10.1007/978-3-319-89689-2_11
M3 - Chapter
C2 - 29916024
AN - SCOPUS:85048960133
T3 - Advances in Neurobiology
SP - 283
EP - 301
BT - Advances in Neurobiology
PB - Springer New York LLC
ER -