J Mov Disord.
2023 Sep;16(3):261-278. 10.14802/jmd.23023.
GBA1 Variants and Parkinson’s Disease: Paving the Way for Targeted Therapy
- Affiliations
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- 1Department of Neurology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
- 2Institute of Neurogenetics, University of Lübeck and University Hospital of Schleswig-Holstein, Lübeck, Germany
- 3Advanced Center for Parkinson’s Disease Research, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
- 4Precision Neurology Program, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
- 5Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- KMID: 2545923
- DOI: http://doi.org/10.14802/jmd.23023
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.
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