Pharmacological inhibition of carnitine palmitoyl transferase 1 inhibits and reverses experimental autoimmune encephalitis in rodents

PloS One
Anne Skøttrup MørkholtJ D Nieland

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease characterized by demyelination and inflammation. Dysregulated lipid metabolism and mitochondrial dysfunction are hypothesized to play a key role in MS. Carnitine Palmitoyl Transferase 1 (CPT1) is a rate-limiting enzyme for beta-oxidation of fatty acids in mitochondria. The therapeutic effect of pharmacological CPT1 inhibition with etomoxir was investigated in rodent models of myelin oligodendrocyte glycoprotein- and myelin basic protein-induced experimental autoimmune encephalitis (EAE). Mice receiving etomoxir showed lower clinical score compared to placebo, however this was not significant. Rats receiving etomoxir revealed significantly lower clinical score and lower body weight compared to placebo group. When comparing etomoxir with interferon-β (IFN-β), IFN-β had no significant therapeutic effects, whereas etomoxir treatment starting at day 1 and 5 significantly improved the clinical scores compared to the IFN-β and the placebo group. Immunohistochemistry and image assessments of brain sections from rats with EAE showed higher myelination intensity and decreased expression of CPT1A in etomoxir-treated rats compared to placebo group. Moreover, etomoxir mediated increased...Continue Reading

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Citations

Mar 30, 2021·Ageing Research Reviews·Rohan GuptaPravir Kumar
May 2, 2021·Communications Biology·Michael Sloth TrabjergJohn Dirk Vestergaard Nieland
Sep 11, 2021·Frontiers in Cell and Developmental Biology·Lin XiongXian Guo

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Methods Mentioned

BETA
confocal microscopy
FACS
flow cytometry
lipidation

Software Mentioned

ImageJ
EAE

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