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KMID : 1197720230160030261
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대한파킨슨병 및 이상운동질환 학회지
2023 Volume.16 No. 3 p.261 ~ p.278
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GBA1 Variants and Parkinson’s Disease: Paving the Way for Targeted Therapy
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Huh Young-Eun
Tatiana Usnich
Clemens R. Scherzer
Christine Klein
Chung Sun-Ju
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Abstract
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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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KEYWORD
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Autophagy lysosomal pathway, β-glucocerebrosidase, ER-Golgi trafficking, GBA1, Parkinson’s disease, Sphingolipid
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