title: ÐÐ°ÑÑÑÐµÐ½Ð¸Ðµ Ð´ÐµÐ¿Ð¾-ÑÐ¿ÑÐ°Ð²Ð»ÑÐµÐ¼Ð¾Ð³Ð¾ Ð²Ñ Ð¾Ð´Ð° ÐºÐ°Ð»ÑÑÐ¸Ñ Ð² Ð¿Ð°ÑÐ¸ÐµÐ½Ñ-ÑÐ¿ÐµÑÐ¸ÑÐ¸ÑÐ½Ð¾Ð¹ Ð¼Ð¾Ð´ÐµÐ»Ð¸ ÑÐ¿Ð¸Ð½Ð¾ÑÐµÑÐµÐ±ÐµÐ»Ð»ÑÑÐ½Ð¾Ð¹ Ð°ÑÐ°ÐºÑÐ¸Ð¸ 17 ÑÐ¸Ð¿Ð°
title: Ð²ÑÐ¿ÑÑÐºÐ½Ð°Ñ ÐºÐ²Ð°Ð»Ð¸ÑÐ¸ÐºÐ°ÑÐ¸Ð¾Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð±Ð°ÐºÐ°Ð»Ð°Ð²ÑÐ°
titleType: Subtitle
title: Violation of store-operated calcium entry in a patient-specific model of spinocerebellar ataxia type 17
Creators: name: ÐÑÐ¸ÑÐ°Ð½Ð¾Ð²Ð°, ÐÐ»ÐµÐ½Ð°
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: 2024
Subjects: Ð½ÐµÐ¹ÑÐ¾Ð´ÐµÐ³ÐµÐ½ÐµÑÐ°ÑÐ¸Ñ
Ð¿Ð¾Ð»Ð¸Ð³Ð»ÑÑÐ°Ð¼Ð¸Ð½Ð¾Ð²ÑÐµ Ð·Ð°Ð±Ð¾Ð»ÐµÐ²Ð°Ð½Ð¸Ñ
Ð¿Ð°ÑÐ¸ÐµÐ½Ñ-ÑÐ¿ÐµÑÐ¸ÑÐ¸ÑÐ½Ð°Ñ Ð¼Ð¾Ð´ÐµÐ»Ñ
ÐºÐ°Ð»ÑÑÐ¸ÐµÐ²Ð°Ñ ÑÐ¸Ð³Ð½Ð°Ð»Ð¸Ð·Ð°ÑÐ¸Ñ
Ð´ÐµÐ¿Ð¾-ÑÐ¿ÑÐ°Ð²Ð»ÑÐµÐ¼ÑÐ¹ Ð²Ñ Ð¾Ð´
neurodegeneration
polyglutamine diseases
patient-specific model
calcium signaling
store-operated entry

description: ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ Ð½Ð°ÑÑÑÐµÐ½Ð¸Ð¹ ÐºÐ°Ð»ÑÑÐ¸ÐµÐ²Ð¾Ð¹ ÑÐµÐ³ÑÐ»ÑÑÐ¸Ð¸ Ð¿ÑÐ¸ ÑÐ¿Ð¸Ð½Ð¾ÑÐµÑÐµÐ±ÐµÐ»Ð»ÑÑÐ½Ð¾Ð¹ Ð°ÑÐ°ÐºÑÐ¸Ð¸ 17-Ð³Ð¾ ÑÐ¸Ð¿Ð° (SCA17) Ð² Ð¿Ð°ÑÐ¸ÐµÐ½ÑÑÐ¿ÐµÑÐ¸ÑÐ¸ÑÐ½ÑÑ Ð¼Ð¾Ð´ÐµÐ»ÑÑ, Ð¿Ð¾Ð»ÑÑÐµÐ½Ð½ÑÑ Ð¸Ð· Ð¸Ð½Ð´ÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÑ Ð¿Ð»ÑÑÐ¸Ð¿Ð¾ÑÐµÐ½ÑÐ½ÑÑ ÑÑÐ²Ð¾Ð»Ð¾Ð²ÑÑ ÐºÐ»ÐµÑÐ¾Ðº (ÐÐÐ¡Ð) Ð¾Ñ Ð·Ð´Ð¾ÑÐ¾Ð²ÑÑ Ð»ÑÐ´ÐµÐ¹ Ð¸ Ð´Ð¾Ð½Ð¾ÑÐ¾Ð² ÑÐ¾ SCA17. ÐÑÐµ Ð´Ð°Ð½Ð½ÑÐµ, Ð¿ÑÐ¸Ð²ÐµÐ´ÐµÐ½Ð½ÑÐµ Ð² ÑÐ°Ð±Ð¾ÑÐµ, Ð¿Ð¾Ð»ÑÑÐµÐ½Ñ Ð½Ð° Ð±Ð°Ð·Ðµ Ð»Ð°Ð±Ð¾ÑÐ°ÑÐ¾ÑÐ¸Ð¸ Ð¸Ð¾Ð½Ð½ÑÑ ÐºÐ°Ð½Ð°Ð»Ð¾Ð² ÐºÐ»ÐµÑÐ¾ÑÐ½ÑÑ Ð¼ÐµÐ¼Ð±ÑÐ°Ð½ Ð² Ð¾ÑÐ´ÐµÐ»Ðµ Ð¼Ð¾Ð»ÐµÐºÑÐ»ÑÑÐ½Ð¾Ð¹ ÑÐ¸Ð·Ð¸Ð¾Ð»Ð¾Ð³Ð¸Ð¸ ÐºÐ»ÐµÑÐºÐ¸ ÐÐ½ÑÑÐ¸ÑÑÑÐ° ÑÐ¸ÑÐ¾Ð»Ð¾Ð³Ð¸Ð¸ Ð ÐÐ. Ð ÑÐµÐ·ÑÐ»ÑÑÐ°ÑÐµ Ð½Ð°ÑÑÐ½Ð¾-Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°ÑÐµÐ»ÑÑÐºÐ¾Ð¹ ÑÐ°Ð±Ð¾ÑÑ Ð±ÑÐ»Ð° Ð½Ð°Ð¹Ð´ÐµÐ½Ð° ÑÑÐ±ÑÐµÐ´Ð¸Ð½Ð¸ÑÐ°, ÐºÐ¾ÑÐ¾ÑÑÑ Ð¼Ñ Ð¿ÑÐµÐ´Ð»Ð°Ð³Ð°ÐµÐ¼ ÑÐ°ÑÑÐ¼Ð°ÑÑÐ¸Ð²Ð°ÑÑ Ð² ÐºÐ°ÑÐµÑÑÐ²Ðµ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»ÑÐ½Ð¾Ð¹ Ð¼Ð¾Ð»ÐµÐºÑÐ»ÑÑÐ½Ð¾Ð¹ Ð¼Ð¸ÑÐµÐ½Ð¸, Ð¾Ð¿ÑÐµÐ´ÐµÐ»ÑÑÑÐµÐ¹ Ð½Ð°ÑÑÑÐµÐ½Ð¸Ðµ Ð´ÐµÐ¿Ð¾ÑÐ¿ÑÐ°Ð²Ð»ÑÐµÐ¼Ð¾Ð³Ð¾ Ð²ÑÐ¾Ð´Ð° ÐºÐ°Ð»ÑÑÐ¸Ñ Ð² ÐÐÐÐÐµÑÐ³Ð¸ÑÐµÑÐºÐ¸Ñ MSNs Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² ÑÐ¾ SCA17. Ð ÑÐ¾Ð´Ðµ ÑÐ°Ð±Ð¾ÑÑ Ð±ÑÐ»Ð¸ ÑÐµÑÐµÐ½Ñ ÑÐ»ÐµÐ´ÑÑÑÐ¸Ðµ Ð·Ð°Ð´Ð°ÑÐ¸: 1. ÑÐµÐ°Ð»Ð¸Ð·Ð¾Ð²Ð°Ð½Ð° Ð´Ð¸ÑÑÐµÑÐµÐ½ÑÐ¸ÑÐ¾Ð²ÐºÐ° Ð¸Ð½Ð´ÑÑÐ¸ÑÐ¾Ð²Ð°Ð½Ð½ÑÑ Ð¿Ð»ÑÑÐ¸Ð¿Ð¾ÑÐµÐ½ÑÐ½ÑÑ ÑÑÐ²Ð¾Ð»Ð¾Ð²ÑÑ ÐºÐ»ÐµÑÐ¾Ðº Ð² ÐÐÐÐÐµÑÐ³Ð¸ÑÐµÑÐºÐ¸Ðµ ÑÑÐµÐ´Ð¸Ð½Ð½ÑÐµ ÑÐ¸Ð¿Ð¸ÐºÐ¾Ð²ÑÐµ Ð½ÐµÐ¹ÑÐ¾Ð½Ñ ÑÑÑÐ¸Ð°ÑÑÐ¼Ð°; 2. Ð±ÑÐ»Ð¸ Ð¿ÑÐ¾Ð²ÐµÐ´ÐµÐ½Ñ ÑÐ»ÐµÐºÑÑÐ¾ÑÐ¸Ð·Ð¸Ð¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¸Ðµ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ Ð¼ÐµÑÐ¾Ð´Ð¾Ð¼ Ð»Ð¾ÐºÐ°Ð»ÑÐ½Ð¾Ð¹ ÑÐ¸ÐºÑÐ°ÑÐ¸Ð¸ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»Ð° patch-clamp Ð² ÐºÐ¾Ð½ÑÐ¸Ð³ÑÑÐ°ÑÐ¸Ð¸ whole-cell Ð¸ Ð¾ÑÐ°ÑÐ°ÐºÑÐµÑÐ¸Ð·Ð¾Ð²Ð°Ð½Ñ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»-Ð·Ð°Ð²Ð¸ÑÐ¸Ð¼ÑÐµ Ð¸ Ð´ÐµÐ¿Ð¾-ÑÐ¿ÑÐ°Ð²Ð»ÑÐµÐ¼ÑÐµ ÑÐ¾ÐºÐ¸; 3. Ð½Ð°Ð¹Ð´ÐµÐ½Ð° Ð¼Ð¾Ð»ÐµÐºÑÐ»ÑÑÐ½Ð°Ñ Ð´ÐµÑÐµÑÐ¼Ð¸Ð½Ð°Ð½ÑÐ°, Ð¾Ð¿Ð¾ÑÑÐµÐ´Ð¾Ð²Ð°Ð²ÑÐ°Ñ Ð°Ð½Ð¾Ð¼Ð°Ð»ÑÐ½Ð¾Ðµ ÑÐ²ÐµÐ»Ð¸ÑÐµÐ½Ð¸Ðµ Ð¿ÑÐ¸ÑÐ¾ÐºÐ¾Ð² ÐºÐ°Ð»ÑÑÐ¸Ñ ÑÐµÑÐµÐ· Ð´ÐµÐ¿Ð¾-Ð·Ð°Ð²Ð¸ÑÐ¸Ð¼ÑÐµ ÐºÐ°Ð½Ð°Ð»Ñ Ð² ÐÐÐÐÐµÑÐ³Ð¸ÑÐµÑÐºÐ¸Ñ ÑÐ¸Ð¿Ð¸ÐºÐ¾Ð²ÑÑ Ð½ÐµÐ¹ÑÐ¾Ð½Ð°Ñ ÑÑÑÐ¸Ð°ÑÑÐ¼Ð°, ÑÐ¿ÐµÑÐ¸ÑÐ¸ÑÐ½ÑÑ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ°Ð¼ ÑÐ¾ SCA17.
description: This work aims to investigate impaired calcium signaling in striatal GABAergic medium spiny neurons (MSNs) specific to spinocerebellar ataxia type 17 (SCA17). The goal of this study is to study and identify calcium dysregulation in patient-specific models derived from induced pluripotent stem cells (iPSCs) from healthy controls and SCA17 donors. All data presented in this work were obtained at the Laboratory of Ion Channels of Cell Membranes in the Department of Molecular Cell Physiology of the Institute of Cytology, Russian Academy of Sciences. As a result of the research work, a subunit was found, which we propose to consider as a potential molecular target that determines the disruption of storeoperated calcium entry in GABAergic MSNs of SCA17 patients. During this study, the following objectives were achieved: 1. differentiation of induced pluripotent stem cells into GABAergic medium spiny striatal neurons was achieved, and the representativeness of this model was confirmed by immunohistochemistry for specific neuronal markers; 2. electrophysiological studies were performed using the whole-cell patch-clamp technique in the local patch-clamp configuration, and voltage-gated calcium currents (VGCCs) and store-operated calcium currents (SOCs) were characterized for GABAergic MSNs from SCA17 patients and healthy donors; 3. a molecular factor has been identified that mediates an abnormal increase in calcium influx through store-operated channels in GABAergic medium spiny striatal neurons, which is specific to patients with SCA17.