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The Ubiquitin System: a Regulatory Hub for Intellectual Disability and Autism Spectrum Disorder

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Abstract

Intellectual disability (ID) and autism spectrum disorder (ASD) are two of the most common neurodevelopmental disorders. Both disorders are extremely heterogenous, and only ~ 40% of reported cases have so far been attributed to genetic mutations. Of the many cellular processes that are affected, the ubiquitin system (UbS) is of particular relevance in that it can rapidly regulate multiple signaling cascades simultaneously. The UbS is a post-translational modification process that revolves around the covalent attachment of a ubiquitin moiety to a substrate, thereby influencing different elements of protein biology, including trafficking, signal transduction, and degradation. Importantly, the UbS has been implicated in regulating multiple pathophysiological pathways related to ASD and ID. This review will discuss how the UbS acts as major signaling hub in the pathogenesis of ASD and ID, raising the prospect of treating broader patient cohorts by targeting the UbS as a common point of convergence of various mutations.

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This work was supported by SFARI Explorer Grant 527556 to M. Piper and S. Wood.

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  1. Stephen A. Wood and Michael Piper contributed equally to this work.

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  1. Griffith Institute for Drug Discovery, Griffith University, Brisbane, Queensland, 4111, Australia

    Maria A. Kasherman, Susitha Premarathne & Stephen A. Wood

  2. The School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, 4072, Australia

    Maria A. Kasherman & Michael Piper

  3. The Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, 4072, Australia

    Thomas H. J. Burne & Michael Piper

  4. Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, Brisbane, Queensland, 4076, Australia

    Thomas H. J. Burne

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Kasherman, M.A., Premarathne, S., Burne, T.H.J. et al. The Ubiquitin System: a Regulatory Hub for Intellectual Disability and Autism Spectrum Disorder. Mol Neurobiol 57, 2179–2193 (2020). https://doi.org/10.1007/s12035-020-01881-x

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