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. 2024 Oct;39(10):1886-1891.
doi: 10.1002/mds.29839. Epub 2024 May 26.

Role of Bβ1 overexpression in the pathogenesis of SCA12

Chengqian Zhou  1 , Fan Tang  1 , Tao Dong  1 , Hans B Liu  1 , Leon Deng  1 , Russell L Margolis  1   2 , Pan P Li  1
Affiliations

Role of Bβ1 overexpression in the pathogenesis of SCA12

Chengqian Zhou et al. Mov Disord. 2024 Oct.

Abstract

Background: Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by a CAG/CTG repeat expansion at the PPP2R2B locus.

Objective: We investigated how the CAG repeat expansion within the PPP2R2B 7B7D transcript influences the expression of Bβ1 and a potential protein containing a long polyserine tract.

Methods: Transcript and protein expression were measured using quantitative PCR (qPCR) and Western blot, respectively, in an SK-N-MC cell model that overexpresses the full-length PPP2R2B 7B7D transcript. The apoptotic effect of a protein containing a long polyserine tract on SK-N-MC cells was evaluated using caspase 3/7 activity.

Results: The CAG repeat expansion increases the expression of the PPP2R2B 7B7D transcript, as well as Bβ1 protein, in an SK-N-MC cell model in which the full-length PPP2R2B 7B7D transcript is overexpressed. The CAG repeat expansion within the 7B7D transcript is translated into a long polyserine tract that triggers apoptosis in SK-N-MC cells.

Conclusions: The SCA12 mutation leads to overexpression of PPP2R2B Bβ1 and to expression of a protein containing a long polyserine tract; both these effects potentially contribute to SCA12 pathogenesis. © 2024 International Parkinson and Movement Disorder Society.

Keywords: Bβ1; polyserine; spinocerebellar ataxia type 12.

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Conflict of interest statement

Relevant conflict of interest/financial disclosure: Nothing to report.

References

    1. Choudhury S et al. Clinical Characterization of Genetically Diagnosed Cases of Spinocerebellar Ataxia Type 12 from India. Mov. Disord. Clin. Pract 5, 39–46 (2017). - PMC - PubMed
    1. Srivastava AK, Takkar A, Garg A & Faruq M Clinical behaviour of spinocerebellar ataxia type 12 and intermediate length abnormal CAG repeats in PPP2R2B. Brain 140, 27–36 (2017). - PubMed
    1. Cohen RL & Margolis RL Spinocerebellar ataxia type 12: clues to pathogenesis. Curr. Opin. Neurol 29, 735–742 (2016). - PubMed
    1. Holmes SE et al. Expansion of a novel CAG trinucleotide repeat in the 5’ region of PPP2R2B is associated with SCA12. Nat. Genet 23, 391–392 (1999). - PubMed
    1. O’Hearn E, Holmes SE & Margolis RL Spinocerebellar ataxia type 12. Handb. Clin. Neurol 103, 535–547 (2012). - PubMed

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