Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 강수성 | * |
dc.date.accessioned | 2019-11-19T16:30:57Z | - |
dc.date.available | 2019-11-19T16:30:57Z | - |
dc.date.issued | 2015 | * |
dc.identifier.issn | 0006-8950 | * |
dc.identifier.issn | 1460-2156 | * |
dc.identifier.other | OAK-25822 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/252046 | - |
dc.description.abstract | Polyglutamine diseases are a class of dominantly inherited neurodegenerative disorders for which there is no effective treatment. Here we provide evidence that activation of serotonergic signalling is beneficial in animal models of Machado-Joseph disease. We identified citalopram, a selective serotonin reuptake inhibitor, in a small molecule screen of FDA-approved drugs that rescued neuronal dysfunction and reduced aggregation using a Caenorhabditis elegans model of mutant ataxin 3-induced neurotoxicity. MOD-5, the C. elegans orthologue of the serotonin transporter and cellular target of citalopram, and the serotonin receptors SER-1 and SER-4 were strong genetic modifiers of ataxin 3 neurotoxicity and necessary for therapeutic efficacy. Moreover, chronic treatment of CMVMJD135 mice with citalopram significantly reduced ataxin 3 neuronal inclusions and astrogliosis, rescued diminished body weight and strikingly ameliorated motor symptoms. These results suggest that small molecule modulation of serotonergic signalling represents a promising therapeutic target for Machado-Joseph disease. | * |
dc.language | English | * |
dc.publisher | OXFORD UNIV PRESS | * |
dc.subject | spinocerebellar ataxia type 3 | * |
dc.subject | ataxin 3 aggregation | * |
dc.subject | therapy | * |
dc.subject | selective serotonin reuptake inhibitor | * |
dc.subject | citalopram | * |
dc.title | Serotonergic signalling suppresses ataxin 3 aggregation and neurotoxicity in animal models of Machado-Joseph disease | * |
dc.type | Article | * |
dc.relation.volume | 138 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.journaltitle | BRAIN | * |
dc.identifier.doi | 10.1093/brain/awv262 | * |
dc.identifier.wosid | WOS:000365135700019 | * |
dc.author.google | Teixeira-Castro, Andreia | * |
dc.author.google | Jalles, Ana | * |
dc.author.google | Esteves, Sofia | * |
dc.author.google | Kang, Soosung | * |
dc.author.google | Santos, Liliana da Silva | * |
dc.author.google | Silva-Fernandes, Anabela | * |
dc.author.google | Neto, Mario F. | * |
dc.author.google | Brielmann, Renee M. | * |
dc.author.google | Bessa, Carlos | * |
dc.author.google | Duarte-Silva, Sara | * |
dc.author.google | Miranda, Adriana | * |
dc.author.google | Oliveira, Stephanie | * |
dc.author.google | Neves-Carvalho, Andreia | * |
dc.author.google | Bessa, Joao | * |
dc.author.google | Summavielle, Teresa | * |
dc.author.google | Silverman, Richard B. | * |
dc.author.google | Oliveira, Pedro | * |
dc.author.google | Morimoto, Richard I. | * |
dc.author.google | Maciel, Patricia | * |
dc.contributor.scopusid | 강수성(56177300500) | * |
dc.date.modifydate | 20240301081003 | * |