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Deciphering the pathophysiological mechanisms underpinning myoclonus dystonia using pluripotent stem cell-derived cellular models

Li, Zongze ORCID: https://orcid.org/0000-0002-9923-7205, Abram, Laura ORCID: https://orcid.org/0009-0005-8078-8209 and Peall, Kathryn ORCID: https://orcid.org/0000-0003-4749-4944 2024. Deciphering the pathophysiological mechanisms underpinning myoclonus dystonia using pluripotent stem cell-derived cellular models. Cells 13 (18) , 1520. 10.3390/cells13181520

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Abstract

Dystonia is a movement disorder with an estimated prevalence of 1.2% and is characterised by involuntary muscle contractions leading to abnormal postures and pain. Only symptomatic treatments are available with no disease- modifying or curative therapy, in large part due to the limited understanding of the underlying pathophysiology. However, the inherited monogenic forms of dystonia provide an opportunity for the development of disease models to examine these mechanisms. Myoclonus DdDystonia , caused by SGCE mutations encoding the ε-sarcoglycan protein, represents one of now >50 monogenic forms. Previous research has implicated the in-volvement of the basal ganglia–cerebello-thalamo-cortical circuit in dystonia pathogenesis, but with further work is needed in to understanding the specific molecular and cellular mechanisms. Plu-ripotent stem cell technology enables a patient-derived disease modelling platform harbouring disease-causing mutations. In this review, we discuss the current understanding of the aetiology of Myoclonus DdDystonia, recent advances in producing distinct neuronal types from pluripotent stem cells, and their application in modelling Myoclonus DdDystonia in vitro. Future research employing pluripotent stem cell-derived cellular models is crucial to elucidate how distinct neuronal types may contribute to dystonia, and how disruption to neuronal function can give rise to dystonic disorders.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: MDPI
ISSN: 2073-4409
Funders: Medical Research Council
Date of First Compliant Deposit: 10 September 2024
Date of Acceptance: 7 September 2024
Last Modified: 15 Oct 2024 14:58
URI: https://orca.cardiff.ac.uk/id/eprint/171977

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