Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by autosomal recessive mutations of the GBA1 gene, which encodes for the lysosomal enzyme glucocerebrosidase (GCase). This enzyme is responsible for cleaving glucosylceramide (GlcCer) and its absence results in detrimental intracellular accumulation of GlcCer. Additionally, while the link remains enigmatic, individuals with heterozygous and homozygous GBA1 mutations have the greatest genetic risk for developing Parkinson’s disease (PD). Indeed, certain patients with common identified GBA1 mutations may manifest substantial neurological symptoms (nGD) and even PD while others are symptom-free. Current research suggests that genetic modifiers and especially epigenetic factors may play a role in determining GD phenotype and severity, as well as onset of PD. Here, we aim to elucidate whether viral infections of the CNS may serve as nGD pathology-modulators in a murine model, and if so, to delineate their mechanism of action. By exposing murine nGD models to viral insult, we aim to determine whether viral infections of the CNS can affect the severity of nGD symptoms and furthermore perpetrate host susceptibility to Parkinsonism.
