Gene Expression of Lysosomal Membrane Proteins in Parkinson Disease, Associated with Mutations in the Glucocerebrosidase Gene (GBA)

Introduction. In carriers of a mutation in the lysosomal enzyme glucocerebrosidase (GBA) gene, the risk of Parkinson disease (PD) is increased by 7–8 times. However, not all carriers of the GBA gene mutations develop PD during their lifetime. We hypothesize that the dysfunction in the lysosomal membrane proteins involved in autophagy and transport of GBA into the lysosomes can contribute to the development of PD in carriers of mutations in the GBA gene.

The aim of the study was to assess the contribution of LAMP2 and SCARB2 genes expression in CD45⁺ peripheral blood cells to the development of GBA-PD.

Materials and methods. We examined 9 patients with GBA-PD, 9 asymptomatic GBA gene mutations carriers, 37 patients with PD, and 56 people in the control group. The relative mRNA level of LAMP2 and SCARB2 genes in CD45⁺ blood cells, obtained using magnetic sorting, was measured by quantitative real-time polymerase chain reaction using fluorescent probes.

Results. The relative mRNA level of LAMP2 and SCARB2 genes in CD45⁺ blood cells was reduced in patients with GBA-PD in comparison to patients with PD and to controls (LAMP2: p<0.0001, p = 0.01 respectively; SCARB2: p = 0.01, p<0.05, respectively) and in asymptomatic carriers of GBA gene mutations compared to patients with PD (LAMP2: p = 0.021; SCARB2: p<0.05) and controls (LAMP2: p = 0.029). We also found decreased mRNA levels of the LAMP2 gene (p = 0.024) and the absence of differences in the mRNA levels of the SCARB2 gene (р<0.05) in CD45⁺ blood cells in patients with GBA-PD when compared to the group of asymptomatic carriers of GBA gene mutations.

Conclusion. GBA-PD is characterized by a pronounced expression of the LAMP2 gene in the CD45⁺ peripheral blood cells, which may indicate a role of the decreased LAMP2 gene expression in the pathogenesis of GBA-PD.