Astroglial conditional Slc13a3 knockout is therapeutic in murine Canavan leukodystrophy.
- Resource Type
- Academic Journal
- Authors
- Hull VL; Department of Neurology, UC Davis School of Medicine, Sacramento, California, USA.; Shriners Hospital for Children, Sacramento, California, USA.; Department of Physiology, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.; Wang Y; Department of Neurology, UC Davis School of Medicine, Sacramento, California, USA.; Shriners Hospital for Children, Sacramento, California, USA.; McDonough J; Department of Biological Sciences, Kent State University, Kent, Ohio, USA.; Zhu M; Department of Neurology, UC Davis School of Medicine, Sacramento, California, USA.; Shriners Hospital for Children, Sacramento, California, USA.; Burns T; Department of Neurology, UC Davis School of Medicine, Sacramento, California, USA.; Shriners Hospital for Children, Sacramento, California, USA.; Al Ramel N; Department of Biological Sciences, Kent State University, Kent, Ohio, USA.; Dehghani A; Department of Neurology, UC Davis School of Medicine, Sacramento, California, USA.; Shriners Hospital for Children, Sacramento, California, USA.; Guo F; Department of Neurology, UC Davis School of Medicine, Sacramento, California, USA.; Shriners Hospital for Children, Sacramento, California, USA.; Pleasure D; Department of Neurology, UC Davis School of Medicine, Sacramento, California, USA.; Shriners Hospital for Children, Sacramento, California, USA.
- Source
- Publisher: Wiley Periodicals, Inc on behalf of American Neurological Association Country of Publication: United States NLM ID: 101623278 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2328-9503 (Electronic) Linking ISSN: 23289503 NLM ISO Abbreviation: Ann Clin Transl Neurol Subsets: MEDLINE
- Subject
- Language
- English
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.
(© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)