Role of Bβ1 overexpression in the pathogenesis of SCA12

Abstract

AbstractBackgroundSpinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by a CAG/CTG repeat expansion at the PPP2R2B locus.ObjectiveWe 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.MethodsTranscript 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.ResultsThe 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.ConclusionsThe 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.