Pathological Role of GBA2 in GBA1-deficient Neuronopathic Gaucher’s Disease Model of Medaka

Background: Recent genetic studies have identified heterozygous mutations in the GBA1 gene as a strong risk factor for sporadic Parkinson’s disease (PD). The GBA1 mutations are responsible for Gaucher’s disease (GD). We have reported that GBA1 knock-out (KO) medaka can survive long enough for pathological analysis of disease progression in contrast to the perinatal death of GBA1 KO mice. Since this neuronopathic GD medaka model displays α-synuclein accumulation, it could be useful to investigate the mechanisms of α-synuclein accumulation in GD and GBA1-related PD. The non-lysosomal β-Glucosidase (GBA2), which is localized at the endoplasmic reticulum and Golgi apparatus, also cleaves glucosylceramide to glucose and ceramide. A recent study has reported that the deletion of GBA2 rescues the visceral manifestation of type1 GD mice model.