title: ÐÐ°ÑÑÑÐµÐ½Ð¸Ðµ Ð°ÑÑÐ¾ÑÐ°Ð³Ð¸Ð¸ Ñ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ GBA-Ð°ÑÑÐ¾ÑÐ¸Ð¸ÑÐ¾Ð²Ð°Ð½Ð½Ð¾Ð¹ Ð±Ð¾Ð»ÐµÐ·Ð½ÑÑ ÐÐ°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð° Ð¸ Ñ Ð±ÐµÑÑÐ¸Ð¼Ð¿ÑÐ¾Ð¼Ð½ÑÑ Ð½Ð¾ÑÐ¸ÑÐµÐ»ÐµÐ¹ Ð¼ÑÑÐ°ÑÐ¸Ð¸ Ð² Ð³ÐµÐ½Ðµ GBA
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: Disturbance of autophagy in patients with GBA-associated Parkinson's disease and asymptomatic carriers of mutations in the GBA gene
Creators: name: ÐÐ·ÑÐ¼ÑÐµÐ½ÐºÐ¾, ÐÑÑÐµÐ¼
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Ð¸Ð·Ð¸ÐºÐ°
Ð±Ð¾Ð»ÐµÐ·Ð½Ñ ÐÐ°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð°
Ð³Ð»ÑÐºÐ¾ÑÐµÑÐµÐ±ÑÐ¾Ð·Ð¸Ð´Ð°Ð·Ð°
Ð³ÐµÐºÑÐ¾Ð·Ð¸Ð»ÑÑÐ¸Ð½Ð³Ð¾Ð·Ð¸Ð½
Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¸ Ð¿ÐµÑÐ¸ÑÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ ÐºÑÐ¾Ð²Ð¸
Ð°ÑÑÐ¾ÑÐ°Ð³Ð¸Ñ
Parkinson's disease
glucocerebrosidase
hexosylsphingosine
peripheral blood macrophages
autophagy

description: ÐÐ¸Ð¿Ð»Ð¾Ð¼Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Â«ÐÐ°ÑÑÑÐµÐ½Ð¸Ðµ Ð°ÑÑÐ¾ÑÐ°Ð³Ð¸Ð¸ Ñ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ GBA-Ð°ÑÑÐ¾ÑÐ¸Ð¸ÑÐ¾Ð²Ð°Ð½Ð½Ð¾Ð¹ Ð±Ð¾Ð»ÐµÐ·Ð½ÑÑ ÐÐ°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð° Ð¸ Ñ Ð±ÐµÑÑÐ¸Ð¼Ð¿ÑÐ¾Ð¼Ð½ÑÑ Ð½Ð¾ÑÐ¸ÑÐµÐ»ÐµÐ¹ Ð¼ÑÑÐ°ÑÐ¸Ð¹ Ð² Ð³ÐµÐ½Ðµ GBAÂ» Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ Ð²Ð»Ð¸ÑÐ½Ð¸Ñ Ð¼ÑÑÐ°ÑÐ¸Ð¹ Ð² Ð³ÐµÐ½Ðµ GBAÂ Ð½Ð° Ð°ÑÑÐ¾ÑÐ°Ð³Ð¸Ñ, Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ ÑÐµÑÐ¼ÐµÐ½ÑÐ° Ð³Ð»ÑÐºÐ¾ÑÐµÑÐµÐ±ÑÐ¾Ð·Ð¸Ð´Ð°Ð·Ñ (GCase) Ð¸ ÑÑÐ¾Ð²ÐµÐ½Ñ Ð»Ð¸Ð·Ð¾ÑÑÐ¸Ð½Ð³Ð¾Ð»Ð¸Ð¿Ð¸Ð´Ð° Ð³ÐµÐºÑÐ¾Ð·Ð¸Ð»ÑÑÐ¸Ð½Ð³Ð¾Ð·Ð¸Ð½Ð° (HexSph) Ð² Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð°Ñ Ð¸ Ð¿ÐµÑÐ¸ÑÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ ÐºÑÐ¾Ð²Ð¸Â Ñ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ GBA-Ð°ÑÑÐ¾ÑÐ¸Ð¸ÑÐ¾Ð²Ð°Ð½Ð½Ð¾Ð¹ Ð±Ð¾Ð»ÐµÐ·Ð½ÑÑ ÐÐ°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð° (GBA-ÐÐ) Ð¸ Ñ Ð±ÐµÑÑÐ¸Ð¼Ð¿ÑÐ¾Ð¼Ð½ÑÑ Ð½Ð¾ÑÐ¸ÑÐµÐ»ÐµÐ¹ Ð¼ÑÑÐ°ÑÐ¸Ð¹ Ð³ÐµÐ½Ð° GBA (GBA-Ð½Ð¾ÑÐ¸ÑÐµÐ»ÐµÐ¹). Ð ÑÐ¾Ð´Ðµ ÑÐ°Ð±Ð¾ÑÑ Ð±ÑÐ»Ð¾ Ð¿ÑÐ¾Ð²ÐµÐ´ÐµÐ½Ð¾ ÐºÑÐ»ÑÑÐ¸Ð²Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð² Ð¿ÐµÑÐ¸ÑÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ ÐºÑÐ¾Ð²Ð¸ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ GBA-ÐÐ, GBA-Ð½Ð¾ÑÐ¸ÑÐµÐ»ÐµÐ¹, Ð° ÑÐ°ÐºÐ¶Ðµ Ð½ÐµÐ²ÑÐ¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸ Ð·Ð´Ð¾ÑÐ¾Ð²ÑÑ Ð¸Ð½Ð´Ð¸Ð²Ð¸Ð´ÑÑÐ¼Ð¾Ð² (ÐºÐ¾Ð½ÑÑÐ¾Ð»Ñ), Ð¿ÑÐ¾Ð²ÐµÐ´ÐµÐ½Ð° Ð¾ÑÐµÐ½ÐºÐ° ÑÑÐµÐ¿ÐµÐ½Ð¸ Ð°ÑÑÐ¾ÑÐ°Ð³Ð¸Ð¸ Ð¸ Ð¸Ð·Ð¼ÐµÑÐµÐ½Ð° ÑÐµÑÐ¼ÐµÐ½ÑÐ°ÑÐ¸Ð²Ð½Ð°Ñ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ GCase Ð¸ ÐºÐ¾Ð½ÑÐµÐ½ÑÑÐ°ÑÐ¸Ñ Ð»Ð¸Ð·Ð¾ÑÑÐ¸Ð½Ð³Ð¾Ð»Ð¸Ð¿Ð¸Ð´Ð° HexSph Ð² Ð¿ÐµÑÐ¸ÑÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ ÐºÑÐ¾Ð²Ð¸ Ð¸ Ð¿ÐµÑÐ²Ð¸ÑÐ½Ð¾Ð¹ ÐºÑÐ»ÑÑÑÑÐµ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð² Ð¼ÐµÑÐ¾Ð´Ð¾Ð¼ ÐºÐ¾Ð¼Ð±Ð¸Ð½Ð¸ÑÐ¾Ð²Ð°Ð½Ð½Ð¾Ð¹ Ð²ÑÑÐ¾ÐºÐ¾ÑÑÑÐµÐºÑÐ¸Ð²Ð½Ð¾Ð¹ Ð¶Ð¸Ð´ÐºÐ¾ÑÑÐ½Ð¾Ð¹ ÑÑÐ¾Ð¼Ð°ÑÐ¾Ð³ÑÐ°ÑÐ¸Ð¸-Ð¼Ð°ÑÑ-ÑÐ¿ÐµÐºÑÑÐ¾Ð¼ÐµÑÑÐ¸Ð¸ (ÐÐ­ÐÐ¥ ÐÐ¡/ÐÐ¡). ÐÐ¸Ð¿Ð»Ð¾Ð¼Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð²ÑÐ¿Ð¾Ð»Ð½ÐµÐ½Ð° Ð½Ð° Ð±Ð°Ð·Ðµ Ð»Ð°Ð±Ð¾ÑÐ°ÑÐ¾ÑÐ¸Ð¸ Ð¼Ð¾Ð»ÐµÐºÑÐ»ÑÑÐ½Ð¾Ð¹ Ð³ÐµÐ½ÐµÑÐ¸ÐºÐ¸ ÑÐµÐ»Ð¾Ð²ÐµÐºÐ° ÐÐÐ¦ Â«ÐÑÑÑÐ°ÑÐ¾Ð²ÑÐºÐ¸Ð¹ Ð¸Ð½ÑÑÐ¸ÑÑÑÂ» - ÐÐÐ¯Ð¤. Ð ÑÐ¾Ð´Ðµ Ð´Ð°Ð½Ð½Ð¾Ð¹ ÑÐ°Ð±Ð¾ÑÑ Ð±ÑÐ»Ð¾ Ð¿Ð¾ÐºÐ°Ð·Ð°Ð½Ð¾, ÑÑÐ¾ Ð¼ÑÑÐ°ÑÐ¸Ð¸ Ð² Ð³ÐµÐ½Ðµ GBAÂ Ð°ÑÑÐ¾ÑÐ¸Ð¸ÑÐ¾Ð²Ð°Ð½Ñ Ñ Ð½Ð°ÑÑÑÐµÐ½Ð¸ÐµÐ¼ Ð°ÑÑÐ¾ÑÐ°Ð³Ð¸Ð¸, ÐºÐ°Ðº Ñ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ GBA-ÐÐ, ÑÐ°Ðº Ð¸ Ñ GBA-Ð½Ð¾ÑÐ¸ÑÐµÐ»ÐµÐ¹. ÐÐ»Ñ GBA-Ð½Ð¾ÑÐ¸ÑÐµÐ»ÐµÐ¹ ÑÑÐ¾ Ð¿Ð¾ÐºÐ°Ð·Ð°Ð½Ð¾ Ð²Ð¿ÐµÑÐ²ÑÐµ. ÐÑÐ¾Ð¼Ðµ ÑÐ¾Ð³Ð¾, Ð±ÑÐ»Ð¾ Ð¿ÑÐ¾Ð´ÐµÐ¼Ð¾Ð½ÑÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð¾, ÑÑÐ¾ Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÑ GCaseÂ Ð¾Ð±ÑÐ°ÑÐ½Ð¾ ÐºÐ¾ÑÑÐµÐ»Ð¸ÑÑÐµÑ Ñ Ð½Ð°ÑÑÑÐµÐ½Ð¸ÐµÐ¼ Ð°ÑÑÐ¾ÑÐ°Ð³Ð¸Ð¸ Ð² Ð¿ÐµÑÐ²Ð¸ÑÐ½Ð¾Ð¹ ÐºÑÐ»ÑÑÑÑÐµ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð² Ð½Ð¾ÑÐ¸ÑÐµÐ»ÐµÐ¹ Ð¼ÑÑÐ°ÑÐ¸Ð¹ Ð² Ð³ÐµÐ½Ðµ GBAÂ Ð½ÐµÐ·Ð°Ð²Ð¸ÑÐ¸Ð¼Ð¾ Ð¾Ñ ÑÑÐ°ÑÑÑÐ° Ð±Ð¾Ð»ÐµÐ·Ð½Ð¸ ÐÐ°ÑÐºÐ¸Ð½ÑÐ¾Ð½Ð°. ÐÑÐ¸ Ð²ÑÐ¿Ð¾Ð»Ð½ÐµÐ½Ð¸Ð¸ Ð´Ð¸Ð¿Ð»Ð¾Ð¼Ð½Ð¾Ð¹ ÑÐ°Ð±Ð¾ÑÑ Ð±ÑÐ»Ð¸ Ð¿ÑÐ¾Ð²ÐµÐ´ÐµÐ½Ñ ÑÐ»ÐµÐ´ÑÑÑÐ¸Ðµ ÑÐºÑÐ¿ÐµÑÐ¸Ð¼ÐµÐ½ÑÑ: ÐºÑÐ»ÑÑÐ¸Ð²Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ðµ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð² Ð¿ÐµÑÐ¸ÑÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ ÐºÑÐ¾Ð²Ð¸, Ð¾ÑÐµÐ½ÐºÐ° ÑÐµÐ½Ð¾ÑÐ¸Ð¿Ð¸ÑÐµÑÐºÐ¾Ð³Ð¾ ÑÐ¾Ð·ÑÐµÐ²Ð°Ð½Ð¸Ñ Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð¾Ð², Ð¾ÑÐµÐ½ÐºÐ° ÑÑÐµÐ¿ÐµÐ½Ð¸ Ð°ÑÑÐ¾ÑÐ°Ð³Ð¸Ð¸ Ð² Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð°Ñ Ð¿ÐµÑÐ¸ÑÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹Â ÐºÑÐ¾Ð²Ð¸,Â Ð¾ÑÐµÐ½ÐºÐ° Ð°ÐºÑÐ¸Ð²Ð½Ð¾ÑÑÐ¸ GCase Ð¸ ÐºÐ¾Ð½ÑÐµÐ½ÑÑÐ°ÑÐ¸Ð¸ HexSph Ð² Ð¼Ð°ÐºÑÐ¾ÑÐ°Ð³Ð°Ñ Ð¸ Ð¿ÐµÑÐ¸ÑÐµÑÐ¸ÑÐµÑÐºÐ¾Ð¹ ÐºÑÐ¾Ð²Ð¸ Ð¼ÐµÑÐ¾Ð´Ð¾Ð¼ ÐÐ­ÐÐ¥ ÐÐ¡/ÐÐ¡, ÑÑÐ°ÑÐ¸ÑÑÐ¸ÑÐµÑÐºÐ°Ñ Ð¾Ð±ÑÐ°Ð±Ð¾ÑÐºÐ° Ð´Ð°Ð½Ð½ÑÑ.
description: The master's degree workÂ "Disturbance of autophagy in patients with GBA-associated Parkinson's disease and asymptomatic carriers of mutations in the GBAÂ gene" is devoted to the study of the effect of mutations in the GBAÂ gene on autophagy, the activity of the enzyme glucocerebrosidase (GCase) and the level of lysosphingolipid hexosylsphingosine (HexSph) in macrophages and peripheral blood in patients with GBA-associated Parkinson's disease (GBA-PD) and in asymptomatic carriers of GBAÂ gene mutations (GBAÂ carriers). In the course of the work, peripheral blood macrophages were cultured in patients with GBA-PD, GBAÂ carriers, as well as neurologically healthy individuals (control), the degree of autophagy was assessed and the enzymatic activity of GCase and HexSph concentration in peripheral blood and primary macrophage culture were measured by combined high-performance liquid chromatography-mass spectrometry (HPLC MS/MS). The master's degree work was carried out on the basis of the laboratory of human molecular genetics of the Petersburg Nuclear Physics Institute (PNPI) named by B.P.Konstantinov of NRC Â«Kurchatov InstituteÂ». In the course of this work, it was shown that mutations in the GBA gene are associated with a disturbance of autophagy, both in patients with GBA-PD and in GBA carriers. This is shown for the first time for GBA carriers. It has been demonstrated that GCase activity is inversely correlated with autophagy disturbance in the primary macrophages culture of carriers of mutations in the GBA gene, regardless of the status of Parkinson's disease. When completing the master's degree work, the following experiments were carried out: cultivation of peripheral blood macrophages, assessment of phenotypic maturation of macrophages, assessment of the degree of autophagy in peripheral blood macrophages, assessment of GCase activity and HexSph concentration in macrophages and peripheral blood by HPLC MS/MS, statistical data processing.