Dysregulated axonal <scp>RNA</scp> translation in amyotrophic lateral sclerosis

<jats:p>Amyotrophic lateral sclerosis (<jats:styled-content style="fixed-case">ALS</jats:styled-content>) is an adult‐onset motor neuron disease that has been associated with a diverse array of genetic changes. Prominent among these are mutations in <jats:styled-content style="fixed-case">RNA</jats:styled-content>‐binding proteins (<jats:styled-content style="fixed-case">RBPs</jats:styled-content>) or repeat expansions that give rise to toxic <jats:styled-content style="fixed-case">RNA</jats:styled-content> species. <jats:styled-content style="fixed-case">RBPs</jats:styled-content> are additionally central components of pathologic aggregates that constitute a disease hallmark, suggesting that dysregulation of <jats:styled-content style="fixed-case">RNA</jats:styled-content> metabolism underlies disease progression. In the context of neuronal physiology, transport of <jats:styled-content style="fixed-case">RNAs</jats:styled-content> and localized <jats:styled-content style="fixed-case">RNA</jats:styled-content> translation in axons are fundamental to neuronal survival and function. Several lines of evidence suggest that axonal <jats:styled-content style="fixed-case">RNA</jats:styled-content> translation is a central process perturbed by various pathogenic events associated with <jats:styled-content style="fixed-case">ALS</jats:styled-content>. Dysregulated translation of specific <jats:styled-content style="fixed-case">RNA</jats:styled-content> groups could underlie feedback effects that connect and reinforce disease manifestations. Among such candidates are <jats:styled-content style="fixed-case">RNAs</jats:styled-content> encoding proteins involved in the regulation of microtubule dynamics. Further understanding of axonally dysregulated <jats:styled-content style="fixed-case">RNA</jats:styled-content> targets and of the feedback mechanisms they induce could provide useful therapeutic insights. <jats:italic>WIREs RNA</jats:italic> 2016, 7:589–603. doi: 10.1002/wrna.1352</jats:p><jats:p>This article is categorized under: <jats:list list-type="explicit-label"> <jats:list-item><jats:p>Translation > Translation Regulation</jats:p></jats:list-item> <jats:list-item><jats:p>RNA Export and Localization > RNA Localization</jats:p></jats:list-item> <jats:list-item><jats:p>RNA in Disease and Development > RNA in Disease</jats:p></jats:list-item> </jats:list></jats:p>