GBA RNAi but not catalytic inhibition of glucocerebrosidase with Conduritol-β-epoxide increases levels of total α-synuclein in SH-SY5Y cells

Abstract

Mutations in the glucocerebrosidase gene are a common genetic risk factor for developing Parkinson’s disease. The reasons why glucocerebrosidase mutations cause an increased life-time risk of developing Parkinson’s disease are not fully understood. Here, we aimed to verify whether glucocerebrosidase activity has an effect on total α-synuclein levels. We use SH-SY5Y and primary cortical cells and expose them to either Conduritol-β-epoxide or siRNA targeting GBA 1. Unexpectedly, RNA interference towards GBA 1 and catalytic inhibition produce different effects on α-synuclein levels in cellular models.