Generate QR code
Open Access
Subscription Access
Effect of a pharmacological chaperone glucocerebrosidase on enzyme activity in mouse brain
https://doi.org/10.25557/2073-7998.2025.06.83-85
Abstract
Biallelic mutations in the GBA1 gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are a common high-risk factor for Parkinson’s disease (PD). Pharmacological chaperones (PCs) are being developed as an approach to treating of PD associated with mutations in the GBA1 gene. Using high performance liquid chromatography coupled with tandem mass spectrometry, we evaluated the enzymatic activity of GCase and the concentration of its substrate, hexosylsphingosine (HexSph), in brain tissue of the C57BL/6 mouse after administration of PCs GCase (ambroxol and N2). We showed an increase in GCase activity and a decrease in HexSph concentration in the brain tissue of mice treated with PCs GCase. For the first time, we have demonstrated the efficacy of PCs GCase N2 in brain tissue from C57BL/6 mice.
Supporting agencies: The research was supported by the Russian Science Foundation grant No. 24-15-00177.
About the Authors
A. O. Lavrinova
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»
Russian Federation
Russian Federation
1, mkr. Orlova Roscha, Gatchina, Leningrad region, 188300
E. A. Demidova
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»
Russian Federation
Russian Federation
1, mkr. Orlova Roscha, Gatchina, Leningrad region, 188300
V. N. Pidyurchina
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»
Russian Federation
Russian Federation
1, mkr. Orlova Roscha, Gatchina, Leningrad region, 188300
A. I. Bezrukova
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»; Pavlov First Saint-Petersburg State Medical University
Russian Federation
Russian Federation
1, mkr. Orlova Roscha, Gatchina, Leningrad region, 188300; 6/8, Lva Tolstogo st., St. Petersburg, 197022
E. V. Sergeeva
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»
Russian Federation
Russian Federation
1, mkr. Orlova Roscha, Gatchina, Leningrad region, 188300
V. V. Kvanchiani
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»
Russian Federation
Russian Federation
1, mkr. Orlova Roscha, Gatchina, Leningrad region, 188300
G. V. Baidakova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechie st., Moscow, 115478
E. Y. Zakharova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1, Moskvorechie st., Moscow, 115478
A. K. Emelyanov
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»; Pavlov First Saint-Petersburg State Medical University
Russian Federation
Russian Federation
1, mkr. Orlova Roscha, Gatchina, Leningrad region, 188300; 6/8, Lva Tolstogo st., St. Petersburg, 197022
S. N. Pchelina
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»; Pavlov First Saint-Petersburg State Medical University
Russian Federation
Russian Federation
1, mkr. Orlova Roscha, Gatchina, Leningrad region, 188300; 6/8, Lva Tolstogo st., St. Petersburg, 197022
References
1. Do J., McKinney C., Sharma P., Sidransky E. Glucocerebrosidase and its relevance to Parkinson disease. Mol Neurodegener. 2019;14(1):36. doi:10.1186/s13024-019-0336-2
2. Hertz E., Chen Y., Sidransky E. Gaucher disease provides a unique window into Parkinson disease pathogenesis. Nat Rev Neurol. 2024;20(9):526-540. doi:10.1038/s41582-024-00999-z
3. den Hollander B., Le H.L., Swart E.L., et al. Clinical and preclinical insights into high-dose ambroxol therapy for Gaucher disease type 2 and 3: A comprehensive systematic review. Mol Genet Metab. 2024;143(1-2):108556. doi:10.1016/j.ymgme.2024.108556
4. Baidakova G.V., Boytsov V.M., Emelianov A.K., et al. Allostericheskiy farmakologicheskiy shaperon, vosstanavlivayushchiy funktsiyu glyukotserebrozidazy. Patent №RU2809824C1 [Allosteric pharmacological chaperone that restores glucocerebrosidase function. Patent No. RU2809824C1]. Published 12/19/2023. (In Russ.)
5. Migdalska-Richards A., Daly L., Bezard E., Schapira A.H. Ambroxol effects in glucocerebrosidase and α-synuclein transgenic mice. Ann Neurol. 2016;80(5):766-775. doi:10.1002/ana.24790
Review
For citations:
Lavrinova A.O., Demidova E.A., Pidyurchina V.N., Bezrukova A.I., Sergeeva E.V., Kvanchiani V.V., Baidakova G.V., Zakharova E.Y., Emelyanov A.K., Pchelina S.N. Effect of a pharmacological chaperone glucocerebrosidase on enzyme activity in mouse brain. Medical Genetics. 2025;24(6):83-85. (In Russ.) https://doi.org/10.25557/2073-7998.2025.06.83-85
Views:
8
Email this article 