title: ÐÑÐµÐ½ÐºÐ° Ð²Ð»Ð¸ÑÐ½Ð¸Ñ Ð¼ÑÑÐ°ÑÐ¸Ð¹ Ð² Ð³ÐµÐ½Ðµ GBA Ð½Ð° ÑÑÑÐµÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ ÑÑÐ°Ð½ÑÐ»Ð¾ÐºÐ°ÑÐ¸Ð¸ ÑÐµÑÐ¼ÐµÐ½ÑÐ° Ð³Ð»ÑÐºÐ¾ÑÐµÑÐµÐ±ÑÐ¾Ð·Ð¸Ð´Ð°Ð·Ñ Ð² Ð»Ð¸Ð·Ð¾ÑÐ¾Ð¼Ñ Ð½Ð° Ð¿ÐµÑÐ²Ð¸ÑÐ½Ð¾Ð¹ ÐºÑÐ»ÑÑÑÑÐµ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð² Ð´Ð¾ Ð¸ Ð¿Ð¾ÑÐ»Ðµ Ð²Ð¾Ð·Ð´ÐµÐ¹ÑÑÐ²Ð¸Ñ ÑÐ°ÑÐ¼Ð°ÐºÐ¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ð¼Ð¸ ÑÐ°Ð¿ÐµÑÐ¾Ð½Ð°Ð¼Ð¸
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¼Ð°Ð³Ð¸ÑÑÑÐ°
titleType: Subtitle
title: Evaluation of the effect of mutations in the gba gene on the efficiency of translocation of the enzyme glucocerebrosidase into lysosomes in primary culture of macrophages before and after exposure to pharmacological chaperones
Creators: name: ÐÐ¾Ð³Ð´Ð°Ð½Ð¾Ð²Ð°, ÐÐ°ÑÑÑ
Publisher: name: Ð¡Ð°Ð½ÐºÑ-ÐÐµÑÐµÑÐ±ÑÑÐ³ÑÐºÐ¸Ð¹ Ð¿Ð¾Ð»Ð¸ÑÐµÑÐ½Ð¸ÑÐµÑÐºÐ¸Ð¹ ÑÐ½Ð¸Ð²ÐµÑÑÐ¸ÑÐµÑ ÐÐµÑÑÐ° ÐÐµÐ»Ð¸ÐºÐ¾Ð³Ð¾
Year: 2022
Subjects: ÐÐ¸Ð¾ÑÐµÑ Ð½Ð¾Ð»Ð¾Ð³Ð¸Ñ
Ð±Ð¾Ð»ÐµÐ·Ð½Ñ ÐÐ¾ÑÐµ
Ð³Ð»ÑÐºÐ¾ÑÐµÑÐµÐ±ÑÐ¾Ð·Ð¸Ð´Ð°Ð·Ð°
Ð»Ð¸Ð·Ð¾ÑÐ¾Ð¼Ñ
ÑÐ°ÑÐ¼Ð°ÐºÐ¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ðµ ÑÐ°Ð¿ÐµÑÐ¾Ð½Ñ
Gaucher's disease
Glucocerebrosidase
lysosome
pharmacological chaperones

description: ÐÐ°Ð³Ð¸ÑÑÐµÑÑÐºÐ°Ñ ÑÐ°Ð±Ð¾ÑÐ° Â«ÐÑÐµÐ½ÐºÐ° Ð²Ð»Ð¸ÑÐ½Ð¸Ñ Ð¼ÑÑÐ°ÑÐ¸Ð¹ Ð² Ð³ÐµÐ½Ðµ GBA Ð½Ð° ÑÑÑÐµÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ ÑÑÐ°Ð½ÑÐ»Ð¾ÐºÐ°ÑÐ¸Ð¸ ÑÐµÑÐ¼ÐµÐ½ÑÐ° Ð³Ð»ÑÐºÐ¾ÑÐµÑÐµÐ±ÑÐ¾Ð·Ð¸Ð´Ð°Ð·Ñ Ð² Ð»Ð¸Ð·Ð¾ÑÐ¾Ð¼Ñ Ð½Ð° Ð¿ÐµÑÐ²Ð¸ÑÐ½Ð¾Ð¹ ÐºÑÐ»ÑÑÑÑÐµ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð² Ð´Ð¾ Ð¸ Ð¿Ð¾ÑÐ»Ðµ Ð²Ð¾Ð·Ð´ÐµÐ¹ÑÑÐ²Ð¸Ñ ÑÐ°ÑÐ¼Ð°ÐºÐ¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ð¼Ð¸ ÑÐ°Ð¿ÐµÑÐ¾Ð½Ð°Ð¼Ð¸Â» Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð¾ÑÐµÐ½ÐºÐµ ÑÑÑÐµÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ð²Ð¾ÑÑÑÐ°Ð½Ð¾Ð²Ð»ÐµÐ½Ð¸Ñ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ð¸ ÑÑÐ°Ð½ÑÐ»Ð¾ÐºÐ°ÑÐ¸Ð¸ ÑÐµÑÐ¼ÐµÐ½ÑÐ° Ð³Ð»ÑÐºÐ¾ÑÐµÑÐµÐ±ÑÐ¾Ð·Ð¸Ð´Ð°Ð·Ñ (GCase) Ð² Ð»Ð¸Ð·Ð¾ÑÐ¾Ð¼Ñ Ð¿ÑÐ¸ Ð²Ð¾Ð·Ð´ÐµÐ¹ÑÑÐ²Ð¸Ð¸ ÑÐ°ÑÐ¼Ð°ÐºÐ¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ð¼Ð¸ ÑÐ°Ð¿ÐµÑÐ¾Ð½Ð°Ð¼Ð¸ (Ð¤Ð¨). Ð ÑÐ¾Ð´Ðµ ÑÐ°Ð±Ð¾ÑÑ Ð±ÑÐ»Ð° Ð¿ÑÐ¾Ð¸Ð·Ð²ÐµÐ´ÐµÐ½Ð° Ð¾ÑÐµÐ½ÐºÐ° ÑÑÑÐµÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ð°Ð»Ð»Ð¾ÑÑÐµÑÐ¸ÑÐµÑÐºÐ¾Ð³Ð¾ Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¾ÑÐ° GCase N07 Ð¸ Ð¿ÑÐµÐ´Ð»Ð¾Ð¶ÐµÐ½Ð½ÑÑ Ð½Ð°Ð¼Ð¸ ÐµÐ³Ð¾ ÑÐ¸Ð¼Ð¸ÑÐµÑÐºÐ¸Ñ Ð¼Ð¾Ð´Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¹ Ð½Ð° Ð¿ÐµÑÐ²Ð¸ÑÐ½Ð¾Ð¹ ÐºÑÐ»ÑÑÑÑÐµ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð² Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ Ð±Ð¾Ð»ÐµÐ·Ð½ÑÑ ÐÐ¾ÑÐµ (ÐÐ) Ð¸ Ð»Ð¸Ñ ÐºÐ¾Ð½ÑÑÐ¾Ð»ÑÐ½Ð¾Ð¹ Ð³ÑÑÐ¿Ð¿Ñ Ð² Ð²Ð¾ÑÑÑÐ°Ð½Ð¾Ð²Ð»ÐµÐ½Ð¸Ð¸ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ Ð¸ ÑÑÐ°Ð½ÑÐ»Ð¾ÐºÐ°ÑÐ¸Ð¸ GCase Ð² Ð»Ð¸Ð·Ð¾ÑÐ¾Ð¼Ñ. Ð ÑÐ¾Ð´Ðµ ÑÐ°Ð±Ð¾ÑÑ Ð±ÑÐ»Ð¸ Ð¾Ð¿ÑÐµÐ´ÐµÐ»ÐµÐ½Ñ Ð½ÐµÑÐ¾ÐºÑÐ¸ÑÐ½ÑÐµ ÐºÐ¾Ð½ÑÐµÐ½ÑÑÐ°ÑÐ¸Ð¸ Ð¸ÑÑÐ»ÐµÐ´ÑÐµÐ¼ÑÑ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ð¹. Ð¢Ð°ÐºÐ¶Ðµ Ð¸ÑÑÐ¾Ð´Ñ Ð¸Ð· Ð¿Ð¾Ð»ÑÑÐµÐ½Ð½ÑÑ Ð´Ð°Ð½Ð½ÑÑ Ð¼Ð¾Ð¶Ð½Ð¾ ÑÐ´ÐµÐ»Ð°ÑÑ Ð²ÑÐ²Ð¾Ð´, ÑÑÐ¾ Ð¿ÑÐµÐ´Ð»Ð¾Ð¶ÐµÐ½Ð½ÑÐµ Ð½Ð°Ð¼Ð¸ ÑÐ¾ÐµÐ´Ð¸Ð½ÐµÐ½Ð¸Ñ Ð»ÑÑÑÐµ Ð¿Ð¾Ð²ÑÑÐ°ÑÑ ÑÑÐ°Ð½ÑÐ»Ð¾ÐºÐ°ÑÐ¸Ñ ÑÐµÑÐ¼ÐµÐ½ÑÐ° GCase Ð² Ð»Ð¸Ð·Ð¾ÑÐ¾Ð¼Ñ Ð½Ð° Ð¿ÐµÑÐ²Ð¸ÑÐ½Ð¾Ð¹ ÐºÑÐ»ÑÑÑÑÐµ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð² Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ ÐÐ, Ð¿ÑÐ¸ ÑÑÐ¾Ð¼ ÑÐ°Ð·Ð»Ð¸ÑÐ¸Ñ Ð² ÑÑÑÐµÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ ÑÐ°Ðº Ð¶Ðµ Ð¾Ð±ÑÑÐ»Ð°Ð²Ð»Ð¸Ð²Ð°ÑÑÑÑ Ð½Ð°Ð»Ð¸ÑÐ¸ÐµÐ¼ ÑÐ°Ð·Ð»Ð¸ÑÐ½ÑÑ Ð¼ÑÑÐ°ÑÐ¸Ð¹ Ð² Ð³ÐµÐ½Ðµ GBA Ñ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ ÐÐ. ÐÑÐ¾Ð²ÐµÐ´ÐµÐ½Ñ ÑÐ»ÐµÐ´ÑÑÑÐ¸Ðµ ÑÐºÑÐ¿ÐµÑÐ¸Ð¼ÐµÐ½ÑÑ: Ð¿Ð¾Ð»ÑÑÐµÐ½Ð¸Ðµ Ð¼Ð¾Ð½Ð¾Ð½ÑÐºÐ»ÐµÐ°ÑÐ½Ð¾Ð¹ ÑÑÐ°ÐºÑÐ¸Ð¸ Ð¸Ð· Ð¿ÐµÑÐ¸ÑÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ ÐºÑÐ¾Ð²Ð¸, ÐºÑÐ»ÑÑÐ¸Ð²Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ Ð¼Ð¾Ð½Ð¾ÑÐ¸ÑÐ¾Ð² Ð¸ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð², Ð¾ÑÐµÐ½ÐºÐ° Ð²ÑÐ¶Ð¸Ð²Ð°ÐµÐ¼Ð¾ÑÑÐ¸ Ð¿ÐµÑÐ²Ð¸ÑÐ½ÑÑ ÐºÑÐ»ÑÑÑÑ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð² Ð¿ÑÐ¸ Ð²Ð¾Ð·Ð´ÐµÐ¹ÑÑÐ²Ð¸Ð¸ Ð°Ð»Ð»Ð¾ÑÑÐµÑÐ¸ÑÐµÑÐºÐµÐ³Ð¾Â  Ð°ÐºÑÐ¸Ð²Ð°ÑÐ¾ÑÐ° GCase N07 Ð¸ ÐµÐ³Ð¾ Ð¼Ð¾Ð´Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¹, Ð¾ÑÐµÐ½ÐºÐ° ÐºÐ¾Ð»Ð¾ÐºÐ°Ð»Ð¸Ð·Ð°ÑÐ¸Ð¸ GCase Ð¸ Ð¼Ð°ÑÐºÐµÑÐ° Ð»Ð¸Ð·Ð¾ÑÐ¾Ð¼ Lamp2 Ð² Ð¿ÐµÑÐ²Ð¸ÑÐ½ÑÑ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð°Ñ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ ÐÐ Ð¸ ÐºÐ¾Ð½ÑÑÐ¾Ð»Ñ Ð¼ÐµÑÐ¾Ð´Ð¾Ð¼ Ð¸Ð¼Ð¼ÑÐ½Ð¾Ð³Ð¸ÑÑÐ¾ÑÐ¸Ð¼Ð¸ÑÐµÑÐºÐ¾Ð³Ð¾ Ð¾ÐºÑÐ°ÑÐ¸Ð²Ð°Ð½Ð¸Ñ, Ð¾ÑÐµÐ½ÐºÐ° ÑÐµÑÐ¼ÐµÐ½ÑÐ°ÑÐ¸Ð²Ð½Ð¾Ð¹ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ GCase Ð¸ ÐºÐ¾Ð½ÑÐµÐ½ÑÑÐ°ÑÐ¸Ð¸ Ð»Ð¸Ð·Ð¾ÑÑÐ¸Ð½Ð³Ð¾Ð»Ð¸Ð¿Ð¸Ð´Ð¾Ð² Ð¼ÐµÑÐ¾Ð´Ð¾Ð¼ ÑÐ°Ð½Ð´ÐµÐ¼Ð½Ð¾Ð¹ Ð¼Ð°ÑÑ-ÑÐ¿ÐµÐºÑÑÐ¾Ð¼ÐµÑÑÐ¸Ð¸ Ð² ÑÑÑÐ¾Ð¼ Ð¿ÑÑÐ½Ðµ ÐºÑÐ¾Ð²Ð¸ Ð¸ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð², ÑÑÐ°ÑÐ¸ÑÑÐ¸ÑÐµÑÐºÐ°Ñ Ð¾Ð±ÑÐ°Ð±Ð¾ÑÐºÐ° Ð´Ð°Ð½Ð½ÑÑ.
description: Master's thesis "Evaluation of the effect of mutations in the gba gene on the efficiency of translocation of the enzyme glucocerebrosidase into lysosomes in primary culture of macrophages before and after exposure to pharmacological chaperones" evaluation of the effectiveness of the restoration of the translocation of the glucocerebrosidase enzyme (GCase) in lysosomes when exposed to pharmacological chaperones (PC). In the course of the work, the effectiveness of the allosteric activator GCase N07 and our proposed foreign modifications for the presence of cultural macrophages in patients with Gaucher disease (GD) and the control group on restoring GCase activity and translocation in lysosomes was evaluated.In the course of the work, non-toxic concentrations of the studied compounds were determined. Also, based on the data obtained, it can be concluded that the compounds proposed by us better increase the translocation of the GCase enzyme into lysosomes on the primary culture of macrophages from patients with GD, while differences in efficiency are also due to the presence of various mutations in the GBA gene in patients with GD. The following experiments were carried out: obtaining a mononuclear surface from peripheral blood, cultivating monocytes and macrophages, assessing the survival of primary culture macrophages under the influence of macrophages of the allosteric activator GCase N07 and its modifications, colocalization of GCase and the lysosome marker Lamp2 in primary macrophages of GD patients and control by immunohistochemical staining, evaluation GCase enzymatic activity and detection of lysosphingolipids by tandem mass spectrometry in dry blood spot and macrophages, statistical data processing.