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Lafora progressive myoclonus epilepsy: Disease mechanism and therapeutic attempts

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Abstract

Lafora disease (LD) is a life-threatening autosomal recessive and progressive neurodegenerative disorder that primarily affects adolescents, resulting in mortality within a decade of onset. The symptoms of LD include epileptic seizures, ataxia, dementia, and psychosis. The underlying pathology involves the presence of abnormal glycogen inclusions in neurons and other tissues, which may contribute to neurodegeneration. LD is caused by loss-of-function mutations in either the EPM2A gene or the NHLRC1 gene. These two genes, respectively, code for laforin phosphatase and malin ubiquitin ligase, and are thought to function, as a functional complex, in diverse cellular pathways. One of the major pathways affected in LD is glycogen metabolism; defects here lead to abnormally higher levels of glycogen and its hyperphosphorylation and aggregation, resulting in the formation of Lafora inclusion bodies. Currently, there is no effective therapy for LD. Studies, particularly from animal models, provide distinct insights into the fundamental mechanisms of diseases and potential avenues for therapeutic interventions. The purpose of this review is to present a comprehensive overview of our current knowledge regarding the disease, its genetics, the animal models that have been developed, and the therapeutic strategies that are being developed based on an understanding of the disease mechanism.

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Acknowledgements

The authors would like to thank the past and present members of the laboratory for their contribution to the Lafora disease biology project.

Funding

Research works on Lafora disease in the authors’ laboratories are supported by the Science and Engineering Research Board (SERB), Department of Science and Technology, Government of India (CRG/2020/001371 and JCB/2022/000007).

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Authors and Affiliations

  1. Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, 208016, India

    Rashmi Parihar & Subramaniam Ganesh

  2. Central Experimental Animal Facility, Indian Institute of Technology, Kanpur, 208016, India

    Rashmi Parihar & Subramaniam Ganesh

  3. Gangwal School of Medical Sciences and Technology, Indian Institute of Technology, Kanpur, 208016, India

    Subramaniam Ganesh

Authors
  1. Rashmi Parihar
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  2. Subramaniam Ganesh
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Contributions

Both RP and SG were involved in the conceptualization, collection of data from literature, and writing of the manuscript.

Corresponding author

Correspondence to Subramaniam Ganesh.

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Corresponding editor: Alok Bhattacharya

This article is part of the Topical Collection: The Rare Genetic Disease Research Landscape in India.

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Parihar, R., Ganesh, S. Lafora progressive myoclonus epilepsy: Disease mechanism and therapeutic attempts. J Biosci 49, 22 (2024). https://doi.org/10.1007/s12038-023-00407-6

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