Spinocerebellar ataxias (SCAs) are a heterogenous group of neurodegenerative disorders which commonly inherited in an autosomal dominant manner. They cause muscle incoordination due to degeneration of the cerebellum and other parts of nervous system. Out of all the characterized (>50) SCAs, 14 SCAs are caused due to microsatellite repeat expansion mutations. Repeat expansions can result in toxic protein gain-of-function, protein loss-of-function, and/or RNA gain-of-function effects. The location and the nature of mutation modulate the underlying disease pathophysiology resulting in varying disease manifestations. Potential toxic effects of these mutations likely affect key major cellular processes such as transcriptional regulation, mitochondrial functioning, ion channel dysfunction and synaptic transmission. Involvement of several common pathways suggests interlinked function of genes implicated in the disease pathogenesis. A better understanding of the shared and distinct molecular pathogenic mechanisms in these diseases is required to develop targeted therapeutic tools and interventions for disease management. The prime focus of this review is to elaborate on how expanded ‘CAG’ repeats contribute to the common modes of neurotoxicity and their possible therapeutic targets in management of such devastating disorders.
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Review Article|
September 05 2023
The molecular mechanisms of spinocerebellar ataxias for DNA repeat expansion in disease
Manish Kumar;
Manish Kumar
*
CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India
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Nishu Tyagi;
Nishu Tyagi
*
CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India
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Mohammed Faruq
CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India
Correspondence: Mohammed Faruq (faruq.mohd@igib.res.in)
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Emerg Top Life Sci (2023) ETLS20230013.
Article history
Received:
April 30 2023
Revision Received:
August 01 2023
Accepted:
August 16 2023
Citation
Manish Kumar, Nishu Tyagi, Mohammed Faruq; The molecular mechanisms of spinocerebellar ataxias for DNA repeat expansion in disease. Emerg Top Life Sci 2023; ETLS20230013. doi: https://doi.org/10.1042/ETLS20230013
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