Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Quick Search
My eDoc
Session History
Support Wiki
Direct access to
document ID:

          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2017 (publ. 2016, arch)     Display Documents

ID: 732094.0, MPI für molekulare Biomedizin / Jahrbuch 2017 (publ. 2016, arch)
Peripheral neuropathy via mutant tRNA synthetases: Inhibition of protein translation provides a possible explanation
Authors:Storkebaum, E.
Date of Publication (YYYY-MM-DD):2016-09
Title of Journal:BioEssays
Issue / Number:9
Start Page:818
End Page:829
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Recent evidence indicates that inhibition of protein translation may be a common pathogenic mechanism for peripheral neuropathy associated with mutant tRNA synthetases (aaRSs). aaRSs are enzymes that ligate amino acids to their cognate tRNA, thus catalyzing the first step of translation. Dominant mutations in five distinct aaRSs cause Charcot-Marie-Tooth (CMT) peripheral neuropathy, characterized by length-dependent degeneration of peripheral motor and sensory axons. Surprisingly, loss of aminoacylation activity is not required for mutant aaRSs to cause CMT. Rather, at least for some mutations, a toxic-gain-of-function mechanism underlies CMT-aaRS. Interestingly, several mutations in two distinct aaRSs were recently shown to inhibit global protein translation in Drosophila models of CMT-aaRS, by a mechanism independent of aminoacylation, suggesting inhibition of translation as a common pathogenic mechanism. Future research aimed at elucidating the molecular mechanisms underlying the translation defect induced by CMT-mutant aaRSs should provide novel insight into the molecular pathogenesis of these incurable diseases.
Free Keywords:Charcot-Marie-Tooth peripheral neuropathy; aminoacylation; animal model; axonal degeneration; gain-of-toxic-function; tRNA synthetase; translation
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Jeanine Müller-Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Faculty of Medicine, University of Munster, Munster, Germany.
Identifiers:ISSN:1521-1878 (Electronic) 0265-9247 (Linking) %R 10.1... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/27352040 [ID No:2]
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.