Estudo da expressão gênica de proteínas relacionadas com o estado tiroidiano durante a rediferenciação de células pluripotentes em neurônios enriqueciso humanos com mutação do MeCP2

• Ano de defesa: 2016
• Autor(a) principal: Souza, Janaina Sena de [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Rett syndrome; Thyroid hormone; Neuron; Ipsc; Igf1; Síndrome de Rett; Célula tronco; Neurônio; Hormônio tiroidiano
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3679820; http://repositorio.unifesp.br/handle/11600/47723

Rett syndrome (RTT; MIM 312750) is a severe neurodegenerative disease that mainly affects girls, and its principal cause is the mutation in the methyl CpG binding protein 2 gene (MECP2), this gene is present in the X chromosome, and is related to epigenetic regulation, metilation. Studies have shown that the insulin-like growth factor 1 (IGF1) can rescue the characteristics of neurons derived of patients with RTT to levels similar to control neurons. The thyroid hormones (TH: T3 and T4) are extremely important hormones for the development and maintenance of the central nervous system, and the control of their production and action should be well regulated. This hormone is produced in the thyroid gland and acts virtually in all tissues. To the entrance of the hormone into the target cells it is necessary that there are specialized transporters, such as MCT8 and MCT10. Inside the cell the main thyroid hormone is T3, but the thyroid gland produces mainly T4 (80%), so there must be a mechanism that converts T4 to T3. The desiodases (DIO 1, 2 and 3) are specialized enzymes that can activate or inactivate the THs to have cellular action. TH genomic action occurs through nuclear receptors that bind to DNA. These receptors, TRalpha 1, TRbeta 1 and TRbeta 2, are central to this genomic action of thyroid hormone. Several studies have shown that a dysregulated TH homeostasis can lead to severe neurodevelopmental problems. Taking into account the importance of THs to neuronal formation, our study aims were to correlate the homeostasis of this hormone with Rett syndrome and tried to verify whether treatment with the hormone can rescue the neurons derived from patients with RTT. We showed that genes related to TH homeostasis are altered not only in neuronal cell stage of development but also during the preceding stages, as pluripotent stem cell and neural progenitor cell. Furthermore, we showed that the action of IGF-1 in RTT neuronal rescue is related to the increased expression of IGF1 receptor in this syndrome and that the neurons respond to IGF1 action due to the presence of TRalpha 3.