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Molecular Mechanisms of Spinocerebellar Ataxia Type 1

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Abstract

Polyglutamine (polyQ) disorders are severe forms of inherited neurodegenerative pathologies caused by the expansion of CAG repeats in specific genes accompanied by abnormal elongation of the polyglutamic residues in the mutant part of the protein, impaired protein-protein interactions, and formation of insoluble amyloid inclusions in neurons. Therapy for these diseases is only symptomatic, and it cannot affect the dynamics of the pathological process. To date, nine polyQ diseases are known: spinocerebellar ataxia type 1, 2, 3, 6, 7, and 17, spino-bulbar muscular atrophy, dentatorubral-pallidoluysian atrophy, and Huntington’s disease. Expansion of trinucleotide repeats can take place during processes of replication, transcription and reparation, though the exact mechanisms are still unclear. There are many ways for CAG expansion resulting in neurodegeneration. Nearly complete penetrance of mutant alleles, severe disabilities after 10–15 years from the disease onset, and lack of effective therapy contribute to consideration of polyQ disorders as a very significant problem actively investigated worldwide. This review is focused on the existing models and molecular mechanisms of spinocerebellar ataxia type 1 (SCA1), one of the polyglutamine disorders, which is caused by expansion of CAG repeats in the ATXN1 gene.

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Funding

The present study was supported by the Russian Science Foundation (project no. 19-15-00425).

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  1. Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency, 119435, Moscow, Russia

    E. A. Volovikov, A. V. Davidenko & M. A. Lagarkova

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  1. E. A. Volovikov
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  2. A. V. Davidenko
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  3. M. A. Lagarkova
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Correspondence to M. A. Lagarkova.

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Translated by A. Kazantseva

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Volovikov, E.A., Davidenko, A.V. & Lagarkova, M.A. Molecular Mechanisms of Spinocerebellar Ataxia Type 1. Russ J Genet 56, 129–141 (2020). https://doi.org/10.1134/S102279542002012X

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