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Nonsense-mediated mRNA decay in neuronal physiology and neurodegeneration

Petrić Howe, Marija; Patani, Rickie; (2023) Nonsense-mediated mRNA decay in neuronal physiology and neurodegeneration. Trends in Neurosciences , 46 (10) pp. 879-892. 10.1016/j.tins.2023.07.001. Green open access

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Abstract

The processes of mRNA export from the nucleus and subsequent mRNA translation in the cytoplasm are of particular relevance in eukaryotic cells. In highly polarised cells such as neurons, finely-tuned molecular regulation of these processes serves to safeguard the spatiotemporal fidelity of gene expression. Nonsense-mediated mRNA decay (NMD) is a cytoplasmic translation-dependent quality control process that regulates gene expression in a wide range of scenarios in the nervous system, including neurodevelopment, learning, and memory formation. Moreover, NMD dysregulation has been implicated in a broad range of neurodevelopmental and neurodegenerative disorders. We discuss how NMD and related aspects of mRNA translation regulate key neuronal functions and, in particular, we focus on evidence implicating these processes in the molecular pathogenesis of neurodegeneration. Finally, we discuss the therapeutic potential and challenges of targeting mRNA translation and NMD across the spectrum of largely untreatable neurological diseases.

Type: Article
Title: Nonsense-mediated mRNA decay in neuronal physiology and neurodegeneration
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.tins.2023.07.001
Publisher version: https://doi.org/10.1016/j.tins.2023.07.001
Language: English
Additional information: © 2023 The Author(s). Published by Elsevier Ltd. under a Creative Commons license (http://creativecommons.org/licenses/by/4.0/).
Keywords: ALS, RNA metabolism, brain, spinal cord, motor neuron
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10174971
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