Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 May;57(5):2179-2193.
doi: 10.1007/s12035-020-01881-x. Epub 2020 Jan 23.

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

Maria A Kasherman  1   2 , Susitha Premarathne  1 , Thomas H J Burne  3   4 , Stephen A Wood #  1 , Michael Piper #  5   6
Affiliations
Review

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

Maria A Kasherman et al. Mol Neurobiol. 2020 May.

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.

Keywords: Autism spectrum disorder; Intellectual disability; TGFβ; USP9X; WNT; mTOR.

PubMed Disclaimer

References

    1. American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders. 5th edn., Washington, DC
    1. Chiurazzi P, Pirozzi F (2016) Advances in understanding – genetic basis of intellectual disability. F1000Research 5:599. https://doi.org/10.12688/f1000research.7134.1 - DOI
    1. Ropers HH, Hamel BCJ (2005) X-linked mental retardation. Nat Rev Genet 6(1):46–57. https://doi.org/10.1038/nrg1501 - DOI - PubMed - PMC
    1. Maulik PK, Mascarenhas MN, Mathers CD, Dua T, Saxena S (2011) Prevalence of intellectual disability: a meta-analysis of population-based studies. Res Dev Disabil 32(2):419–436. https://doi.org/10.1016/j.ridd.2010.12.018 - DOI - PubMed - PMC
    1. McKenzie K, Milton M, Smith G, Ouellette-Kuntz H (2016) Systematic review of the prevalence and incidence of intellectual disabilities: current trends and issues. Curr Dev Disord Rep 3(2):104–115. https://doi.org/10.1007/s40474-016-0085-7 - DOI

MeSH terms