Autor(es):
Nóbrega, Clévio ; Conceição, André Francisco da ; Costa, Rafael G ; Koppenol, Rebekah ; Sequeira, Raquel L ; Nunes, Ricardo ; Carmo-Silva, Sara ; Marcelo, Adriana ; Matos, Carlos A. ; Betuing, Sandrine ; Caboche, Jocelyne ; Cartier, Nathalie ; Alves, Sandro
Data: 2020
Identificador Persistente: https://hdl.handle.net/10316/105836
Origem: Estudo Geral - Universidade de Coimbra
Assunto(s): CYP46A1; Cholesterol; Neuroblastoma cells; Huntingtin; Autophagy; Animals; Cell Line, Tumor; Cells, Cultured; Cholesterol 24-Hydroxylase; Huntingtin Protein; Huntington Disease; Mice; Mutant Proteins; Autophagy; Neuroblastoma
Descrição
Objective: Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington’s disease (HD). Following our previous studies in HD, in this study we aim to investigate in vitro in a neuroblastoma cellular model of HD, the effect of CYP46A1 overexpression, an essential enzyme in cholesterol metabolism, on huntingtin aggregation and levels. Results: We found that CYP46A1 reduces the quantity and size of mutant huntingtin aggregates in cells, as well as the levels of mutant huntingtin protein. Additionally, our results suggest that the observed beneficial effects of CYP46A1 in HD cells are linked to the activation of autophagy. Taken together, our results further demonstrate that CYP46A1 is a pertinent target to counteract HD progression.
This work was supported by Brainvectis and E.rare: E-Rare Joint Transna‑ tional Call for Proposals 2017 “Transnational Research Projects for Innovative Therapeutic Approaches for Rare Diseases”. CN laboratory is supported by the French Muscular Dystrophy Association (AFM-Téléthon), the Ataxia UK, and the Fundação para a Ciência e Tecnologia (project ALG-01-0145-FEDER-29480 “SeGrPolyQ”). AM is supported by a Ph.D. fellowship from FCT (SFRH/ BD/133192/2017).
