Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Neuropathol Appl Neurobiol ; 49(2): e12892, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36798010

RESUMO

The European Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative (ESMI) is a consortium established with the ambition to set up the largest European longitudinal trial-ready cohort of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD), the most common autosomal dominantly inherited ataxia worldwide. A major focus of ESMI has been the identification of SCA3/MJD biomarkers to enable future interventional studies. As biosample collection and processing variables significantly impact the outcomes of biomarkers studies, biosampling procedures standardisation was done previously to study visit initiation. Here, we describe the ESMI consensus biosampling protocol, developed within the scope of ESMI, that ultimately might be translated to other neurodegenerative disorders, particularly ataxias, being the first step to protocol harmonisation in the field.


Assuntos
Ataxia Cerebelar , Doença de Machado-Joseph , Ataxias Espinocerebelares , Degenerações Espinocerebelares , Humanos , Biomarcadores
2.
Sci Adv ; 8(47): eabq6324, 2022 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36417521

RESUMO

Evidence from patients with Parkinson's disease (PD) and our previously reported α-synuclein (SNCA) transgenic rat model support the idea that increased SNCA protein is a substantial risk factor of PD pathogenesis. However, little is known about the transcription control of the human SNCA gene in the brain in vivo. Here, we identified that the DYT6 gene product THAP1 (THAP domain-containing apoptosis-associated protein 1) and its interaction partner CTCF (CCCTC-binding factor) act as transcription regulators of SNCA. THAP1 controls SNCA intronic enhancers' activities, while CTCF regulates its enhancer-promoter loop formation. The SNCA intronic enhancers present neurodevelopment-dependent activities and form enhancer clusters similar to "super-enhancers" in the brain, in which the PD-associated single-nucleotide polymorphisms are enriched. Deletion of the SNCA intronic enhancer clusters prevents the release of paused RNA polymerase II from its promoter and subsequently reduces its expression drastically in the brain, which may provide new therapeutic approaches to prevent its accumulation and thus related neurodegenerative diseases defined as synucleinopathies.


Assuntos
Encéfalo , Doença de Parkinson , Humanos , alfa-Sinucleína/genética , Proteínas Reguladoras de Apoptose/metabolismo , Encéfalo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Íntrons/genética , Doença de Parkinson/metabolismo , Polimorfismo de Nucleotídeo Único , Sequências Reguladoras de Ácido Nucleico
3.
Stem Cell Res ; 30: 171-174, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29936336

RESUMO

A skin biopsy of a patient with spinocerebellar ataxia type 3 (SCA3, also known as Machado-Joseph disease (MJD)) caused by a CAG trinucleotide repeat expansion in the ATXN3 gene, was used to generate an induced pluripotent stem cell line, HIHCNi002-A (iPSC-SCA3). Skin fibroblasts were reprogrammed using episomal plasmids carrying hOCT4, hSOX2, hKLF4, hL-MYC, and hLIN28. The iPSC-SCA3 line exhibits chromosomal stability with conservation of the ATXN3 repeat expansion, expresses pluripotency markers and differentiates into endo-, meso-, and ectodermal cells in vitro.


Assuntos
Ataxina-3/genética , Ataxina-3/metabolismo , Doença de Machado-Joseph/genética , Adulto , Diferenciação Celular , Linhagem Celular , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Doença de Machado-Joseph/metabolismo , Doença de Machado-Joseph/patologia , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA