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Trabjerg, Michael Sloth; Andersen, Dennis Christian; Huntjens, Pam; Mørk, Kasper; Warming, Nikolaj; Kullab, Ulla Bismark; Skjønnemand, Marie-Louise Nibelius; Oklinski, Michal Krystian; Oklinski, Kirsten Egelund; Bolther, Luise; Kroese, Lona J.; Pritchard, Colin E. J.; Huijbers, Ivo J.; Corthals, Angelique; Søndergaard, Mads Toft; Kjeldal, Henrik Bech; Pedersen, Cecilie Fjord Morre; Nieland, John Dirk Vestergaard

Inhibition of carnitine palmitoyl-transferase 1 is a potential target in a mouse model of Parkinson’s disease

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  • Media type: E-Article
  • Title: Inhibition of carnitine palmitoyl-transferase 1 is a potential target in a mouse model of Parkinson’s disease
  • Contributor: Trabjerg, Michael Sloth; Andersen, Dennis Christian; Huntjens, Pam; Mørk, Kasper; Warming, Nikolaj; Kullab, Ulla Bismark; Skjønnemand, Marie-Louise Nibelius; Oklinski, Michal Krystian; Oklinski, Kirsten Egelund; Bolther, Luise; Kroese, Lona J.; Pritchard, Colin E. J.; Huijbers, Ivo J.; Corthals, Angelique; Søndergaard, Mads Toft; Kjeldal, Henrik Bech; Pedersen, Cecilie Fjord Morre; Nieland, John Dirk Vestergaard
  • imprint: Springer Science and Business Media LLC, 2023
  • Published in: npj Parkinson's Disease
  • Language: English
  • DOI: 10.1038/s41531-023-00450-y
  • ISSN: 2373-8057
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Glucose metabolism is dysregulated in Parkinson’s disease (PD) causing a shift toward the metabolism of lipids. Carnitine palmitoyl-transferase 1A (CPT1A) regulates the key step in the metabolism of long-chain fatty acids. The aim of this study is to evaluate the effect of downregulating CPT1, either genetically with a <jats:italic>Cpt1a</jats:italic> P479L mutation or medicinally on PD using chronic rotenone mouse models using C57Bl/6J and <jats:italic>Park2</jats:italic> knockout mice. We show that <jats:italic>Cpt1a</jats:italic> P479L mutant mice are resistant to rotenone-induced PD, and that inhibition of CPT1 is capable of restoring neurological function, normal glucose metabolism, and alleviate markers of PD in the midbrain. Furthermore, we show that downregulation of lipid metabolism via CPT1 alleviates pathological motor and non-motor behavior, oxidative stress, and disrupted glucose homeostasis in <jats:italic>Park2</jats:italic> knockout mice. Finally, we confirm that rotenone induces gut dysbiosis in C57Bl/6J and, for the first time, in <jats:italic>Park2</jats:italic> knockout mice. We show that this dysbiosis is alleviated by the downregulation of the lipid metabolism via CPT1.</jats:p>
  • Access State: Open Access