Sun Joo Cha, Ja Hoon Yoon, Yeo Jeong Han, Kiyoung Kim
{"title":"谷胱甘肽s -转移酶的敲低导致cabeza在大脑中的错误定位和积累,cabeza是果蝇FUS的同源物。","authors":"Sun Joo Cha, Ja Hoon Yoon, Yeo Jeong Han, Kiyoung Kim","doi":"10.1080/01677063.2022.2149747","DOIUrl":null,"url":null,"abstract":"<p><p>Glutathione S-transferase omega (GSTO) is an antioxidant enzyme involved in reducing oxidative stress. Recent studies suggest that polymorphic variants of GSTOs affect the onset age and progression of neurodegenerative diseases. Although GSTO activity may affect the development and age dependency of several diseases, the mechanism by which GSTO inactivation in neurons regulates the susceptibility to neurodegenerative diseases is unclear. In the present study, <i>GstO2</i> knockdown in <i>Drosophila</i> led to increased levels of Cabeza (Caz) protein in neurons in an age-dependent manner. <i>Drosophila</i> Caz is the ortholog of human FUS, which is associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We found that cytoplasmic Caz mislocalization and aggregation in neurons significantly increased after <i>GstO2</i> knockdown <i>in vivo</i>. Downregulation of <i>GstO2</i> decreased the solubility of the Caz protein in aging neurons. These findings demonstrate that GSTO is a critical modulator of the development of neurodegenerative diseases by regulating Caz localization and aggregation in the nervous system of <i>Drosophila</i>.</p>","PeriodicalId":16491,"journal":{"name":"Journal of neurogenetics","volume":"37 1-2","pages":"20-24"},"PeriodicalIF":1.8000,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"2","resultStr":"{\"title\":\"Knockdown of glutathione S-transferase leads to mislocalization and accumulation of cabeza, a <i>drosophila</i> homolog of FUS, in the brain.\",\"authors\":\"Sun Joo Cha, Ja Hoon Yoon, Yeo Jeong Han, Kiyoung Kim\",\"doi\":\"10.1080/01677063.2022.2149747\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Glutathione S-transferase omega (GSTO) is an antioxidant enzyme involved in reducing oxidative stress. Recent studies suggest that polymorphic variants of GSTOs affect the onset age and progression of neurodegenerative diseases. Although GSTO activity may affect the development and age dependency of several diseases, the mechanism by which GSTO inactivation in neurons regulates the susceptibility to neurodegenerative diseases is unclear. In the present study, <i>GstO2</i> knockdown in <i>Drosophila</i> led to increased levels of Cabeza (Caz) protein in neurons in an age-dependent manner. <i>Drosophila</i> Caz is the ortholog of human FUS, which is associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We found that cytoplasmic Caz mislocalization and aggregation in neurons significantly increased after <i>GstO2</i> knockdown <i>in vivo</i>. Downregulation of <i>GstO2</i> decreased the solubility of the Caz protein in aging neurons. These findings demonstrate that GSTO is a critical modulator of the development of neurodegenerative diseases by regulating Caz localization and aggregation in the nervous system of <i>Drosophila</i>.</p>\",\"PeriodicalId\":16491,\"journal\":{\"name\":\"Journal of neurogenetics\",\"volume\":\"37 1-2\",\"pages\":\"20-24\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2023-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of neurogenetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/01677063.2022.2149747\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neurogenetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/01677063.2022.2149747","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Knockdown of glutathione S-transferase leads to mislocalization and accumulation of cabeza, a drosophila homolog of FUS, in the brain.
Glutathione S-transferase omega (GSTO) is an antioxidant enzyme involved in reducing oxidative stress. Recent studies suggest that polymorphic variants of GSTOs affect the onset age and progression of neurodegenerative diseases. Although GSTO activity may affect the development and age dependency of several diseases, the mechanism by which GSTO inactivation in neurons regulates the susceptibility to neurodegenerative diseases is unclear. In the present study, GstO2 knockdown in Drosophila led to increased levels of Cabeza (Caz) protein in neurons in an age-dependent manner. Drosophila Caz is the ortholog of human FUS, which is associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We found that cytoplasmic Caz mislocalization and aggregation in neurons significantly increased after GstO2 knockdown in vivo. Downregulation of GstO2 decreased the solubility of the Caz protein in aging neurons. These findings demonstrate that GSTO is a critical modulator of the development of neurodegenerative diseases by regulating Caz localization and aggregation in the nervous system of Drosophila.
期刊介绍:
The Journal is appropriate for papers on behavioral, biochemical, or cellular aspects of neural function, plasticity, aging or disease. In addition to analyses in the traditional genetic-model organisms, C. elegans, Drosophila, mouse and the zebrafish, the Journal encourages submission of neurogenetic investigations performed in organisms not easily amenable to experimental genetics. Such investigations might, for instance, describe behavioral differences deriving from genetic variation within a species, or report human disease studies that provide exceptional insights into biological mechanisms