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- Title
Aminoacyl‐tRNA synthetases in Charcot–Marie–Tooth disease: A gain or a loss?
- Authors
Zhang, Han; Zhou, Zhong‐Wei; Sun, Litao
- Abstract
Charcot‐Marie‐Tooth disease (CMT) is one of the most common inherited neurodegenerative disorders with an increasing number of CMT‐associated variants identified as causative factors, however, there has been no effective therapy for CMT to date. Aminoacyl‐tRNA synthetases (aaRS) are essential enzymes in translation by charging amino acids onto their cognate tRNAs during protein synthesis. Dominant monoallelic variants of aaRSs have been largely implicated in CMT. Some aaRSs variants affect enzymatic activity, demonstrating a loss‐of‐function property. In contrast, loss of aminoacylation activity is neither necessary nor sufficient for some aaRSs variants to cause CMT. Instead, accumulating evidence from CMT patient samples, animal genetic studies or protein conformational analysis has pinpointed toxic gain‐of‐function of aaRSs variants in CMT, suggesting complicated mechanisms underlying the pathogenesis of CMT. In this review, we summarize the latest advances in studies on CMT‐linked aaRSs, with a particular focus on their functions. The current challenges, future direction and the promising candidates for potential treatment of CMT are also discussed.
- Subjects
AMINOACYL-tRNA synthetases; CHARCOT-Marie-Tooth disease; PROTEIN synthesis; PROTEIN analysis; NEURODEGENERATION; CONFORMATIONAL analysis; TRANSFER RNA
- Publication
Journal of Neurochemistry, 2021, Vol 157, Issue 3, p351
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.15249