GBA1 Variants and Parkinson’s Disease: Paving the Way for Targeted Therapy
- Author:
Young Eun HUH
1
;
Tatiana USNICH
;
Clemens R. SCHERZER
;
Christine KLEIN
;
Sun Ju CHUNG
Author Information
- Publication Type:2
- From:Journal of Movement Disorders 2023;16(3):261-278
- CountryRepublic of Korea
- Language:English
- Abstract: Glucosylceramidase beta 1 (GBA1) variants have attracted enormous attention as the most promising and important genetic candidates for precision medicine in Parkinson’s disease (PD). A substantial correlation between GBA1 genotypes and PD phenotypes could inform the prediction of disease progression and promote the development of a preventive intervention for individuals at a higher risk of a worse disease prognosis. Moreover, the GBA1-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. These perspectives have led to the development of novel disease-modifying therapies for PD targeting the GBA1-regulated pathway by repositioning treatment strategies for Gaucher’s disease. This review summarizes the current hypotheses on a mechanistic link between GBA1 variants and PD and possible therapeutic options for modulating GBA1-regulated pathways in PD patients.
