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Polyglutamine diseases

Bunting, EL; Hamilton, J; Tabrizi, SJ; (2022) Polyglutamine diseases. Current Opinion in Neurobiology , 72 pp. 39-47. 10.1016/j.conb.2021.07.001. (In press).

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Bunting_PolyGlutamine Diseases Review Manuscript Final Edits.pdf - Accepted version
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Bunting_Table 1 - Summary table of PolyGlutamine diseases.pdf - Accepted version
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Bunting_Figure 1 - Role of MMR genes and FAN1 in somatic expansion.pdf - Accepted version
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Bunting_Figure 2 - Mechanism of HTT incomplete splicing.pdf - Accepted version
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Bunting_Figure 3 - Pathogenic mechanisms in polyglutamine diseases.pdf - Accepted version
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Abstract

Polyglutamine diseases are a collection of nine CAG trinucleotide expansion disorders, presenting with a spectrum of neurological and clinical phenotypes. Recent human, mouse and cell studies of Huntington's disease have highlighted the role of DNA repair genes in somatic expansion of the CAG repeat region, modifying disease pathogenesis. Incomplete splicing of the HTT gene has also been shown to occur in humans, with the resulting exon 1 fragment most probably contributing to the Huntington's disease phenotype. In the spinocerebellar ataxias, studies have converged on transcriptional dysregulation of ion channels as a key disease modifier. In addition, advances have been made in understanding how increased levels of toxic, polyglutamine-expanded proteins can arise in the spinocerebellar ataxias through post-transcriptional and -translational modifications and autophagic mechanisms. Recent studies in spinal and bulbar muscular atrophy implicate similar pathogenic pathways to the more common polyglutamine diseases, highlighting autophagy stimulation as a potential therapeutic target. Finally, the therapeutic use of antisense oligonucleotides in several polyglutamine diseases has shown preclinical benefits and serves as potential future therapies in humans.

Type: Article
Title: Polyglutamine diseases
DOI: 10.1016/j.conb.2021.07.001
Publisher version: http://dx.doi.org/10.1016/j.conb.2021.07.001
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Polyglutamine, Repeat expansion, CAG repeat, Huntington’s disease, Spinal and bulbar muscular atrophy, Spinocerebellar ataxias
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 > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10134510
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