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Downregulating carnitine palmitoyl transferase 1 affects disease progression in the SOD1 G93A mouse model of ALS.
- Source :
-
Communications biology [Commun Biol] 2021 Apr 30; Vol. 4 (1), pp. 509. Date of Electronic Publication: 2021 Apr 30. - Publication Year :
- 2021
-
Abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease characterized by death of motor neurons. The etiology and pathogenesis remains elusive despite decades of intensive research. Herein, we report that dysregulated metabolism plays a central role in the SOD1 G93A mouse model mimicking ALS. Specifically, we report that the activity of carnitine palmitoyl transferase 1 (CPT1) lipid metabolism is associated with disease progression. Downregulation of CPT1 activity by pharmacological and genetic methods results in amelioration of disease symptoms, inflammation, oxidative stress and mitochondrial function, whereas upregulation by high-fat diet or corticosterone results in a more aggressive disease progression. Finally, we show that downregulating CPT1 shifts the gut microbiota communities towards a protective phenotype in SOD1 G93A mice. These findings reveal that metabolism, and specifically CPT1 lipid metabolism plays a central role in the SOD1 G93A mouse model and shows that CPT1 might be a therapeutic target in ALS.
- Subjects :
- Amyotrophic Lateral Sclerosis metabolism
Amyotrophic Lateral Sclerosis pathology
Animals
Disease Progression
Down-Regulation
Enzyme Inhibitors pharmacology
Female
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Amyotrophic Lateral Sclerosis drug therapy
Carnitine O-Palmitoyltransferase antagonists & inhibitors
Disease Models, Animal
Epoxy Compounds pharmacology
Gastrointestinal Microbiome
Mutation
Superoxide Dismutase-1 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2399-3642
- Volume :
- 4
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Communications biology
- Publication Type :
- Academic Journal
- Accession number :
- 33931719
- Full Text :
- https://doi.org/10.1038/s42003-021-02034-z