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- Loss-of-Function Variant in the SMPD1 Gene in Progressive Supranuclear Palsy-Richardson Syndrome Patients of Chinese Ancestry
- Shen-Yang Lim, Ai Huey Tan, Jia Nee Foo, Yi Jayne Tan, Elaine GY Chew, Azlina Ahmad Annuar, Alfand Marl Dy Closas, Azalea Pajo, Jia Lun Lim, Yi Wen Tay, Anis Nadhirah, Jia Wei Hor, Tzi Shin Toh, Lei Cheng Lit, Jannah Zulkefli, Su Juen Ngim, Weng Khong Lim, Huw R. Morris, Eng-King Tan, Adeline SL Ng
- J Mov Disord. 2024;17(2):213-217. Published online January 31, 2024
- DOI: https://doi.org/10.14802/jmd.24009
- 9,572 View
- 116 Download
- 6 Web of Science
- 6 Crossref
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Abstract
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Supplementary Material - Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson’s disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann–Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.
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Citations
Citations to this article as recorded by
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Piotr Alster, Natalia Madetko-Alster
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Shen-Yang Lim, Anthony E. Lang
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Martin Michaud, Wladimir Mauhin, Thomas Villeneuve, Olivier Lidove
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Shen-Yang Lim, Christine Klein
Journal of Parkinson’s Disease.2024; 14(3): 467. CrossRef - Identification of Genetic Variants in Progressive Supranuclear Palsy in Southeast Asia
Adeline Su Lyn Ng, Ai Huey Tan, Yi Jayne Tan, Jia Lun Lim, Michelle Mulan Lian, Alfand Marl Dy Closas, Azlina Ahmad‐Annuar, Shanthi Viswanathan, Yuen Kang Chia, Jia Nee Foo, Weng Khong Lim, Eng‐King Tan, Shen‐Yang Lim
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- The Genetic Background of the Immunological and Inflammatory Aspects of Progressive Supranuclear Palsy
Review Article
- GBA1 Variants and Parkinson’s Disease: Paving the Way for Targeted Therapy
- Young Eun Huh, Tatiana Usnich, Clemens R. Scherzer, Christine Klein, Sun Ju Chung
- J Mov Disord. 2023;16(3):261-278. Published online June 12, 2023
- DOI: https://doi.org/10.14802/jmd.23023
- 20,719 View
- 653 Download
- 31 Web of Science
- 31 Crossref
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Abstract
PDF
- 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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Citations
Citations to this article as recorded by- Polymeric nanoparticle-mediated GBA1 gene therapy is neuroprotective in a preclinical model of Parkinson’s disease
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