Astroglial conditional Slc13a3 knockout is therapeutic in murine Canavan leukodystrophy.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
28 Jan 2024
28 Jan 2024
Historique:
revised:
22
12
2023
received:
15
09
2023
accepted:
19
01
2024
medline:
29
1
2024
pubmed:
29
1
2024
entrez:
28
1
2024
Statut:
aheadofprint
Résumé
Canavan disease is a leukodystrophy caused by ASPA mutations that diminish oligodendroglial aspartoacylase activity, and is characterized by markedly elevated brain concentrations of the aspartoacylase substrate N-acetyl-l-aspartate (NAA) and by astroglial and intramyelinic vacuolation. Astroglia express NaDC3 (encoded by SLC13A3), a sodium-coupled transporter for NAA and other dicarboxylates. Astroglial conditional Slc13a3 deletion in aspartoacylase-deficient Canavan disease model mice ("CD mice") reversed brain NAA elevation and improved motor function. These results demonstrate that astroglial NaDC3 contributes to brain NAA elevation in CD mice, and suggest that suppressing astroglial NaDC3 activity would ameliorate human Canavan disease.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : R21NS117386
Pays : United States
Organisme : NIH HHS
ID : R21NS133881
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR001861
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001860
Pays : United States
Informations de copyright
© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
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