The role of autoimmunity in narcolepsy

• Autor(a) principal: Gonçalves, Paulo Sérgio Pereira
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/8632
• topic: Autoimmunity; Hypersomnia; Narcolepsy; Orexins; Sleep Disorders; Domínio/Área Científica::Ciências Médicas::Ciências da Saúde::Medicina

Narcolepsy is a lifelong hypersomnia with low prevalence worldwide. Narcoleptic patients have been highly associated with HLA-DQB1*06:02 which triggered an interest in the autoimmune possibility of this disorder’s onset. Through the improvement of both technologies and techniques, further associations and hints of its mechanism were found, allowing for a continuous improvement on the knowledge of the disorder. The discovery of orexins and orexinergic neurons was a major breakthrough that gave scientists the chance of focusing efforts on a specific cell. The later association with T cell receptors further suggested autoimmunity, but the lack of an autoantigen or inflammatory markers in narcoleptics suggested that that was not the case. However, research continued and what could be later proven as another major breakthrough was just discovered, namely the C-amidated form of orexin. This molecule is secreted by orexinergic neurons and its half-life is short due to the C-terminal peptidase mediated degradation. It has been found to have high affinities toward DQ0602, showing that it could be the autoantigen scientists have been looking for.