Aminoacyl-tRNA synthetases in Charcot-Marie-Tooth disease: A gain or a loss?

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 pinp

SUBMITTER: Zhang H 

PROVIDER: S-EPMC8247414 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature