Human Peripheral Blood Macrophages As a Model for Studying Glucocerebrosidase Dysfunction

M. A. Nikolaev; A. E. Kopytova; G. V. Baidakova; A. K. Emel’yanov; G. N. Salogub; K. A. Senkevich; T. S. Usenko; M. V. Gorchakova; Yu. P. Koval’chuk; O. A. Berkovich; E. Yu. Zakharova; S. N. Pchelina

doi:10.1134/S1990519X19020081

Human Peripheral Blood Macrophages As a Model for Studying Glucocerebrosidase Dysfunction

Authors: Nikolaev M.A.¹^,2, Kopytova A.E.¹, Baidakova G.V.³, Emel’yanov A.K.¹^,2, Salogub G.N.⁴, Senkevich K.A.¹^,2, Usenko T.S.¹^,2, Gorchakova M.V.², Koval’chuk Y.P.², Berkovich O.A.², Zakharova E.Y.³, Pchelina S.N.¹^,2
Affiliations:
1. St. Petersburg Konstantinov Institute of Nuclear Physics, National Research Center Kurchatov Institute
2. Pavlov First St. Petersburg State Medical University
3. Research Center of Medical Genetics
4. Almazov National Medical Research Center, Ministry of Health of the Russian Federation
Issue: Vol 13, No 2 (2019)
Pages: 100-106
Section: Article
URL: https://journals.rcsi.science/1990-519X/article/view/212886
DOI: https://doi.org/10.1134/S1990519X19020081
ID: 212886

Cite item

Full Text

Open Access
Restricted Access

Access granted
Restricted Access

Subscription Access

Abstract
About the authors
References
Statistics

Abstract

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.

Keywords

Gaucher’s disease, macrophages, glucocerebrosidase, lysosphingolipids

Username
Password
Remember me

Forgot password?	Register

Username
Password
Remember me

Forgot password?	Register

Human Peripheral Blood Macrophages As a Model for Studying Glucocerebrosidase Dysfunction

Full Text

Abstract

Keywords

About the authors

This website uses cookies