Отправить статью по E-mail Human Peripheral Blood Macrophages As a Model for Studying Glucocerebrosidase Dysfunction
- Авторы: Nikolaev M.1,2, Kopytova A.1, Baidakova G.3, Emel’yanov A.1,2, Salogub G.4, Senkevich K.1,2, Usenko T.1,2, Gorchakova M.2, Koval’chuk Y.2, Berkovich O.2, Zakharova E.3, Pchelina S.1,2
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Учреждения:
- St. Petersburg Konstantinov Institute of Nuclear Physics, National Research Center Kurchatov Institute
- Pavlov First St. Petersburg State Medical University
- Research Center of Medical Genetics
- Almazov National Medical Research Center, Ministry of Health of the Russian Federation
- Выпуск: Том 13, № 2 (2019)
- Страницы: 100-106
- Раздел: Article
- URL: https://journals.rcsi.science/1990-519X/article/view/212886
- DOI: https://doi.org/10.1134/S1990519X19020081
- ID: 212886
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Аннотация
Decreased activity of glucocerebrosidase (GCase) as a result of mutations in the GBA gene causes Gaucher’s disease (GD), which belongs to the group of lysosomal storage disorders. The risk of Parkinson’s disease in homo- and heterozygous carriers of GBA mutations is elevated seven- to eightfold. Screening of novel compounds designed to enhance GCase activity requires development of in vitro models based on primary cell cultures obtained from patients carrying GBA mutations. In this work, the efficiency of different methods used to culture peripheral blood macrophages of GD patients and control subjects was compared, and GCase activity and lysosphingolipid concentrations were evaluated using tandem mass spectrometry (HPLC‒MS/MS) in dried cell spots. For the first time, the efficacy of restoring the activity of mutant GCase has been assessed in primary macrophages of GD patients cultured in the presence of pharmacological GCase chaperones isofagomine and ambroxol. Based on these results, a convenient method of in vitro screening of candidate pharmacological agents designed to increase GCase activity can be proposed.
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Об авторах
M. Nikolaev
St. Petersburg Konstantinov Institute of Nuclear Physics, National Research Center Kurchatov Institute; Pavlov First St. Petersburg State Medical University
Автор, ответственный за переписку.
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, Gatchina, Leningrad oblast, 188300; St. Petersburg, 197022
A. Kopytova
St. Petersburg Konstantinov Institute of Nuclear Physics, National Research Center Kurchatov Institute
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, Gatchina, Leningrad oblast, 188300
G. Baidakova
Research Center of Medical Genetics
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, Moscow, 115522
A. Emel’yanov
St. Petersburg Konstantinov Institute of Nuclear Physics, National Research Center Kurchatov Institute; Pavlov First St. Petersburg State Medical University
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, Gatchina, Leningrad oblast, 188300; St. Petersburg, 197022
G. Salogub
Almazov National Medical Research Center, Ministry of Health of the Russian Federation
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, St. Petersburg, 197341
K. Senkevich
St. Petersburg Konstantinov Institute of Nuclear Physics, National Research Center Kurchatov Institute; Pavlov First St. Petersburg State Medical University
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, Gatchina, Leningrad oblast, 188300; St. Petersburg, 197022
T. Usenko
St. Petersburg Konstantinov Institute of Nuclear Physics, National Research Center Kurchatov Institute; Pavlov First St. Petersburg State Medical University
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, Gatchina, Leningrad oblast, 188300; St. Petersburg, 197022
M. Gorchakova
Pavlov First St. Petersburg State Medical University
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, St. Petersburg, 197022
Yu. Koval’chuk
Pavlov First St. Petersburg State Medical University
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, St. Petersburg, 197022
O. Berkovich
Pavlov First St. Petersburg State Medical University
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, St. Petersburg, 197022
E. Zakharova
Research Center of Medical Genetics
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, Moscow, 115522
S. Pchelina
St. Petersburg Konstantinov Institute of Nuclear Physics, National Research Center Kurchatov Institute; Pavlov First St. Petersburg State Medical University
Email: Nikolaev_MA@pnpi.nrcki.ru
Россия, Gatchina, Leningrad oblast, 188300; St. Petersburg, 197022
