The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's disease

• Main Author: Nóbrega, Clévio
• Publication Date: 2020
• Other Authors: 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
• Format: Article
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: https://hdl.handle.net/10316/105836; https://doi.org/10.1186/s13104-020-05053-x
• topic: CYP46A1; Cholesterol; Neuroblastoma cells; Huntingtin; Autophagy; Animals; Cell Line, Tumor; Cells, Cultured; Cholesterol 24-Hydroxylase; Huntingtin Protein; Huntington Disease; Mice; Mutant Proteins; Autophagy; Neuroblastoma

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.