Targeted down-regulation of Hipp1 ameliorates tau-induced deficits in Drosophila melanogaster  

作　　者：Sung Yeon Park Jieun Seo Seulbee Lee Joohyung Kim Sang Jeong Kim Seungbok Lee Yang-Sook Chun 

机构地区：[1]Ischemic/Hypoxic Disease Institute,Seoul National University College of Medicine,Seoul 03080,Republic of Korea [2]Department of Biomedical Sciences,Seoul National University College of Medicine,Seoul 03080,Republic of Korea [3]Department of Physiology,Seoul National University College of Medicine,Seoul 03080,Republic of Korea [4]Department of Brain and Cognitive Sciences,Seoul National University,Seoul 08826,Republic of Korea [5]Department of Cell and Developmental Biology and Dental Research Institute,Seoul National University,Seoul 08826,Republic of Korea

出　　处：《Genes & Diseases》2023年第6期2248-2251,共4页基因与疾病（英文）

基　　金：supported by the National Research Foundation grants from the Korean government(No.2016R1D1A1A02937353,2018R1D1A1B07042756,2018R1A5A2025964,2019R1A2C2083886,2021R1I1A1A01044744);Jieun Seo and Seulbee Lee received a scholarship from the BK21-plus education program of the National Research Foundation of Korea.

摘　　要：Tauopathies,such as Alzheimer's disease(AD),are neurodegenerative diseases characterized by the deposition of neurofibrillary tangles comprising hyperphosphorylated tau protein in the human brain.1 Given that abnormal epigenetic alterations in heterochromatin configuration have been documented in AD patients and transgenic animal models of AD,2 we investigated the roles of novel heterochromatin-associated interactors3 in tauopathies.Using transgenic flies via UAS-Gal4 binary system,we found that knockdown of Hipp1(HP1a and insulator partner protein-1)3 ameliorates.tauR4ow(referred to as"tau"hereafter for simplicity)2-induced locomotion defects,reduced lifespan,and degeneration of brain tissues.Intriguingly,Hipp1 knockdown restored tau-driven aberrant expression of putative insulator targets and aberrant insulator-mediated epigenetic alterations.HIPP1 may have a role as an insulator-binding partner regarding being implicated in tauinduced neurodegeneration.

关 键 词：TAU alterations DEGENERATION 

分 类 号：R74[医药卫生—神经病学与精神病学]