Cholesterol redistribution triggered by CYP46A1 gene therapy improves major hallmarks of Niemann-Pick type C disease but is not sufficient to halt neurodegeneration.
Brain cholesterol metabolism
CYP46A1
Gene therapy
Neurodegeneration
Niemann pick type C disorders
Journal
Biochimica et biophysica acta. Molecular basis of disease
ISSN: 1879-260X
Titre abrégé: Biochim Biophys Acta Mol Basis Dis
Pays: Netherlands
ID NLM: 101731730
Informations de publication
Date de publication:
22 Dec 2023
22 Dec 2023
Historique:
received:
21
07
2023
revised:
13
12
2023
accepted:
14
12
2023
medline:
25
12
2023
pubmed:
25
12
2023
entrez:
24
12
2023
Statut:
aheadofprint
Résumé
Cholesterol 24-hydroxylase (CYP46A1) is an exclusively neuronal cytochrome P450 enzyme responsible for converting cholesterol into 24S-hydroxycholesterol, which serves as the primary pathway for eliminating cholesterol in the brain. We and others have shown that increased activity of CYP46A1 leads to reduced levels of cholesterol and has a positive effect on cognition. Therefore, we hypothesized that CYP46A1 could be a potential therapeutic target in Niemann-Pick type C (NPC) disease, a rare and fatal neurodegenerative disorder, characterized by cholesterol accumulation in endolysosomal compartments. Herein, we show that CYP46A1 ectopic expression, in cellular models of NPC and in Npc1
Identifiants
pubmed: 38142760
pii: S0925-4439(23)00359-9
doi: 10.1016/j.bbadis.2023.166993
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
166993Informations de copyright
Copyright © 2023. Published by Elsevier B.V.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nathalie Cartier is a founder of BrainVectis. All other authors declare not to disclose any financial interest from the present research work.