title: Study of the Huntingtonâs disease pathogenesis with primary dermal fibroblasts of patients
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: ÐÐ·ÑÑÐµÐ½Ð¸Ðµ Ð¿Ð°ÑÐ¾Ð³ÐµÐ½ÐµÐ·Ð° Ð±Ð¾Ð»ÐµÐ·Ð½Ð¸ Ð¥Ð°Ð½ÑÐ¸Ð½Ð³ÑÐ¾Ð½Ð° Ð¿ÑÐ¸ Ð¿Ð¾Ð¼Ð¾ÑÐ¸ Ð¿ÐµÑÐ²Ð¸ÑÐ½ÑÑ Ð´ÐµÑÐ¼Ð°Ð»ÑÐ½ÑÑ ÑÐ¸Ð±ÑÐ¾Ð±Ð»Ð°ÑÑÐ¾Ð² Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð²
Creators: name: ÐÐ°Ð±Ñ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: 2023
Subjects: Ð±Ð¾Ð»ÐµÐ·Ð½Ñ ÐÐµÐ½ÑÐ¸Ð½Ð³ÑÐ¾Ð½Ð°
ÑÐ¸Ð±ÑÐ¾Ð±Ð»Ð°ÑÑÑ
Ð¼Ð¸ÑÐ¾Ñ Ð¾Ð½Ð´ÑÐ¸Ð¸
ÑÐ½Ð´Ð¾Ð¿Ð»Ð°Ð·Ð¼Ð°ÑÐ¸ÑÐµÑÐºÐ¸Ð¹ ÑÐµÑÐ¸ÐºÑÐ»ÑÐ¼
ÐÐ¾Ð»Ð¸Ð
Huntingtons disease
fibroblasts
mitochondria
endoplasmic reticulum
PolyQ

description: ÐÐ°Ð½Ð½Ð°Ñ ÑÐ°Ð±Ð¾ÑÐ° Ð¿Ð¾ÑÐ²ÑÑÐµÐ½Ð° Ð²ÑÑÐ²Ð»ÐµÐ½Ð¸Ñ Ð¿Ð°ÑÐ¾Ð»Ð¾Ð³Ð¸ÑÐµÑÐºÐ¾Ð³Ð¾ ÑÐµÐ½Ð¾ÑÐ¸Ð¿Ð° Ð±Ð¾Ð»ÐµÐ·Ð½Ð¸ ÐÐµÐ½ÑÐ¸Ð½Ð³ÑÐ¾Ð½Ð° Ð½Ð° ÐºÐ»ÐµÑÐ¾ÑÐ½Ð¾Ð¼ ÑÑÐ¾Ð²Ð½Ðµ Ð¿ÑÐ¸ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ð¸ Ð¿ÐµÑÐ²Ð¸ÑÐ½ÑÑ Ð´ÐµÑÐ¼Ð°Ð»ÑÐ½ÑÑ ÑÐ¸Ð±ÑÐ¾Ð±Ð»Ð°ÑÑÐ¾Ð² Ð±Ð¾Ð»ÑÐ½ÑÑ. Ð ÑÐ°Ð±Ð¾ÑÐµ Ð¸ÑÐ¿Ð¾Ð»ÑÐ·Ð¾Ð²Ð°Ð½Ñ Ð¼ÐµÑÐ¾Ð´Ñ ÐºÑÐ»ÑÑÐ¸Ð²Ð¸ÑÐ¾Ð²Ð°Ð½Ð¸Ñ ÐºÐ»ÐµÑÐ¾Ðº Ð¿ÐµÑÐ²Ð¸ÑÐ½ÑÑ Ð´ÐµÑÐ¼Ð°Ð»ÑÐ½ÑÑ ÑÐ¸Ð±ÑÐ¾Ð±Ð»Ð°ÑÑÐ¾Ð² ÑÐµÐ»Ð¾Ð²ÐµÐºÐ°, Ð¸Ð¼Ð¼ÑÐ½Ð¾ÑÐ»ÑÐ¾ÑÐµÑÑÐµÐ½ÑÐ½Ð¾Ðµ Ð¾ÐºÑÐ°ÑÐ¸Ð²Ð°Ð½Ð¸Ðµ, Ð²ÐµÑÑÐµÑÐ½-Ð±Ð»Ð¾ÑÑÐ¸Ð½Ð³. Ð ÑÑÐ¾Ð¼ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ð¸ Ð¼Ñ ÑÑÐ¿ÐµÑÐ½Ð¾ Ð²Ð¸Ð·ÑÐ°Ð»Ð¸Ð·Ð¸ÑÐ¾Ð²Ð°Ð»Ð¸ Htt Ñ Ð¿Ð¾Ð¼Ð¾ÑÑÑ Ð¸Ð¼Ð¼ÑÐ½Ð¾ÑÐ»ÑÐ¾ÑÐµÑÑÐµÐ½ÑÐ½Ð¾Ð³Ð¾ Ð¾ÐºÑÐ°ÑÐ¸Ð²Ð°Ð½Ð¸Ñ PolyQ, ÐºÐ¾ÑÐ¾ÑÐ¾Ðµ Ð¿Ð¾ÐºÐ°Ð·Ð°Ð»Ð¾ Ð½ÐµÐ·Ð½Ð°ÑÐ¸ÑÐµÐ»ÑÐ½Ð¾Ðµ ÑÐ²ÐµÐ»Ð¸ÑÐµÐ½Ð¸Ðµ ÑÑÐ¾Ð²Ð½Ñ PolyQ Ð² ÑÐ¸Ð±ÑÐ¾Ð±Ð»Ð°ÑÑÐ°Ñ Ð¿Ð°ÑÐ¸ÐµÐ½ÑÐ¾Ð² Ñ ÐÐ¥ Ð¿Ð¾ ÑÑÐ°Ð²Ð½ÐµÐ½Ð¸Ñ Ñ ÑÐ¸Ð±ÑÐ¾Ð±Ð»Ð°ÑÑÐ°Ð¼Ð¸ Ð·Ð´Ð¾ÑÐ¾Ð²ÑÑ Ð´Ð¾Ð½Ð¾ÑÐ¾Ð². ÐÐ¾Ð²ÑÑÐµÐ½Ð¸Ðµ ÑÑÐ¾Ð²Ð½Ñ Ð¾ÐºÐ¸ÑÐ»ÐµÐ½Ð½Ð¾Ð³Ð¾ 8-Ð³Ð¸Ð´ÑÐ¾ÐºÑÐ¸-2-Ð´ÐµÐ·Ð¾ÐºÑÐ¸Ð³ÑÐ°Ð½Ð¾Ð·Ð¸Ð½Ð° (8-OHDG) Ð½Ðµ Ð½Ð°Ð±Ð»ÑÐ´Ð°Ð»Ð¾ÑÑ Ð² ÑÐ¸Ð±ÑÐ¾Ð±Ð»Ð°ÑÑÐ°Ñ Ð±Ð¾Ð»ÑÐ½ÑÑ ÐÐ¥ Ð¿Ð¾ ÑÑÐ°Ð²Ð½ÐµÐ½Ð¸Ñ Ñ ÑÐ¸Ð±ÑÐ¾Ð±Ð»Ð°ÑÑÐ°Ð¼Ð¸ Ð·Ð´Ð¾ÑÐ¾Ð²ÑÑ Ð´Ð¾Ð½Ð¾ÑÐ¾Ð². ÐÐ½Ð°Ð»Ð¸Ð· Ð¿Ð¾ÐºÐ°Ð·Ð°Ð» Ð±Ð¾Ð»ÐµÐµ Ð²ÑÑÐ¾ÐºÐ¸Ðµ ÑÑÐ¾Ð²Ð½Ð¸ GRP75 Ð² Ð·Ð´Ð¾ÑÐ¾Ð²ÑÑ ÑÐ¸Ð±ÑÐ¾Ð±Ð»Ð°ÑÑÐ°Ñ, ÑÐµÐ¼ Ð² ÑÐ¸Ð±ÑÐ¾Ð±Ð»Ð°ÑÑÐ°Ñ HD, Ñ Ð¿Ð¾ÑÑÐ¸ Ð·Ð½Ð°ÑÐ¸Ð¼ÑÐ¼Ð¸ Ð´Ð°Ð½Ð½ÑÐ¼Ð¸ Ð¸ ÑÐ½Ð¸Ð¶ÐµÐ½Ð¸ÐµÐ¼ ÑÑÐ¾Ð²Ð½ÐµÐ¹ S1R, ÑÑÐ¾ Ð¼Ð¾Ð¶ÐµÑ ÑÐºÐ°Ð·ÑÐ²Ð°ÑÑ Ð½Ð° Ð½Ð°ÑÑÑÐµÐ½Ð¸Ðµ ÑÐµÐ³ÑÐ»ÑÑÐ¸Ð¸ ÑÐ¸Ð³Ð½Ð°Ð»ÑÐ½ÑÑ Ð¿ÑÑÐµÐ¹ Ca2+. Ð ÐµÐ·ÑÐ»ÑÑÐ°ÑÑ Ð¸ÑÑÐ»ÐµÐ´Ð¾Ð²Ð°Ð½Ð¸Ñ Ð¿ÑÐ¾Ð»Ð¸Ð²Ð°ÑÑ ÑÐ²ÐµÑ Ð½Ð° Ð¸Ð·Ð¼ÐµÐ½ÐµÐ½Ð¸Ñ Ð¾ÐºÐ¸ÑÐ»Ð¸ÑÐµÐ»ÑÐ½Ð¾Ð³Ð¾ ÑÑÑÐµÑÑÐ° Ð¸ Ð±ÐµÐ»ÐºÐ¾Ð²ÑÐµ ÐºÐ¾Ð½ÑÐ°ÐºÑÑ Ð¼ÐµÐ¶Ð´Ñ Ð­Ð  Ð¸ Ð¼Ð¸ÑÐ¾ÑÐ¾Ð½Ð´ÑÐ¸ÑÐ¼Ð¸ Ð¿ÑÐ¸ ÐÐ¥, ÑÑÐ¾ Ð¼Ð¾Ð¶ÐµÑ ÑÐ¿Ð¾ÑÐ¾Ð±ÑÑÐ²Ð¾Ð²Ð°ÑÑ Ð»ÑÑÑÐµÐ¼Ñ Ð¿Ð¾Ð½Ð¸Ð¼Ð°Ð½Ð¸Ñ Ð¼ÐµÑÐ°Ð½Ð¸Ð·Ð¼Ð¾Ð² Ð·Ð°Ð±Ð¾Ð»ÐµÐ²Ð°Ð½Ð¸Ñ Ð¸ Ð¼Ð¸ÑÐµÐ½ÐµÐ¹ Ð´Ð»Ñ Ð¿Ð¾ÑÐµÐ½ÑÐ¸Ð°Ð»ÑÐ½ÑÑ Ð»ÐµÐºÐ°ÑÑÑÐ².
description: The given work is devoted Detection of the pathological phenotype of Huntingtons disease at the cellular level in the study of primary dermal fibroblasts of patients. The methods used in this work are cell culturing of primary human dermal fibroblasts, immunofluorescent staining, western blotting. In this study, we successfully visualized Htt through PolyQ immunofluorescence staining which showed non-significant increase in PolyQ level in HD patientsâ fibroblasts comparing to healthy donorsâ fibroblasts. Increased levels of oxidized 8-hydroxy-2-deoxyguanosine (8-OHDG) were not observed in fibroblasts from HD patients compared to fibroblasts from healthy donors. Analysis showed higher levels of GRP75 in healthy fibroblasts than HD fibroblasts with almost significant data and decrease of S1R levels which may mark impaired Ca2+Â  signaling pathways dysregulation. The results of the study shed light on oxidative stress changes and protein contacts between ER and mitochondria in HD which may contribute to better understanding of the disease mechanisms and targets for potential drugs.