Glucocerebrosidase (GBA) variants have been attracting enormous attention as the most promising and important genetic candidate for precision medicine in Parkinson’s disease (PD). A substantial correlation between the GBA genotype and PD phenotype informs the prediction of disease progression and may promote the development of a preventive intervention for individuals at a higher risk of a worse disease prognosis. Moreover, the GBA-regulated pathway provides new perspectives on the pathogenesis of PD, such as dysregulated sphingolipid metabolism, impaired protein quality control, and disrupted endoplasmic reticulum-Golgi trafficking. This has led to the development of novel disease-modifying therapies for PD targeting the GBA-regulated pathway by repositioning treatment strategies for Gaucher’s disease. This review summarizes the current hypotheses on a mechanistic link between GBA variants and PD and possible therapeutic options modulating GBA-regulated pathways in PD patients.

PMID 37302978