Role of Bβ1 overexpression in the pathogenesis of SCA12.

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) Role of Bβ1 overexpression in the pathogenesis of SCA12 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.