Dysregulation of metabolic pathways by carnitine palmitoyl-transferase 1 plays a key role in central nervous system disorders: experimental evidence based on animal models
| العنوان: | Dysregulation of metabolic pathways by carnitine palmitoyl-transferase 1 plays a key role in central nervous system disorders: experimental evidence based on animal models |
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| المؤلفون: | Kasper Mørk, Michael Sloth Trabjerg, Parisa Gazerani, Michal K. Oklinski, Jacek Lichota, Anne Skøttrup Mørkholt, Ivo J. Huijbers, Dennis Christian Andersen, Lona Kroese, John Nieland, Angelique Corthals, Colin Pritchard, Katrine Jønsson, Marie Louise Nibelius Skjønnemand |
| المصدر: | Trabjerg, M S, Mørkholt, A S, Lichota, J, Oklinski, M K E, Andersen, D C, Jønsson, K, Mørk, K, Skjønnemand, M-L N, Kroese, L J, Pritchard, C E J, Huijbers, I J, Gazerani, P, Corthals, A & Nieland, J D V 2020, ' Dysregulation of metabolic pathways by carnitine palmitoyl-transferase 1 plays a key role in central nervous system disorders : experimental evidence based on animal models ', Scientific Reports, vol. 10, no. 1, 15583 . https://doi.org/10.1038/s41598-020-72638-8Test Scientific Reports, Vol 10, Iss 1, Pp 1-19 (2020) Scientific Reports Trabjerg, M S, Mørkholt, A S, Lichota, J, Oklinski, M K E, Andersen, D C, Jønsson, K, Mørk, K, Skjønnemand, M L N, Kroese, L J, Pritchard, C E J, Huijbers, I J, Gazerani, P, Corthals, A & Nieland, J D V 2020, ' Dysregulation of metabolic pathways by carnitine palmitoyl-transferase 1 plays a key role in central nervous system disorders : experimental evidence based on animal models ', Scientific Reports, vol. 10, no. 1, 15583 . https://doi.org/10.1038/s41598-020-72638-8Test |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Encephalomyelitis, Autoimmune, Experimental, Central nervous system, lcsh:Medicine, Drug development, Disease, Biology, Article, Rats, Sprague-Dawley, Mice, Superoxide Dismutase-1, Rotenone, medicine, Animals, Motor neuron disease, Carnitine, Amyotrophic lateral sclerosis, lcsh:Science, Multidisciplinary, Carnitine O-Palmitoyltransferase, Multiple sclerosis, Neurodegenerative diseases, lcsh:R, Neurodegeneration, Brain, Parkinson Disease, medicine.disease, Gastrointestinal Microbiome, Rats, Demyelinating diseases, Experimental models of disease, Metabolic pathway, medicine.anatomical_structure, Preclinical research, Mutation, Experimental pathology, Female, lcsh:Q, Neuroscience, Metabolic Networks and Pathways, medicine.drug |
| الوصف: | The etiology of CNS diseases including multiple sclerosis, Parkinson’s disease and amyotrophic lateral sclerosis remains elusive despite decades of research resulting in treatments with only symptomatic effects. In this study, we provide evidence that a metabolic shift from glucose to lipid is a key mechanism in neurodegeneration. We show that, by downregulating the metabolism of lipids through the key molecule carnitine palmitoyl transferase 1 (CPT1), it is possible to reverse or slowdown disease progression in experimental models of autoimmune encephalomyelitis-, SOD1G93A and rotenone models, mimicking these CNS diseases in humans. The effect was seen both when applying a CPT1 blocker or by using a Cpt1a P479L mutant mouse strain. Furthermore, we show that diet, epigenetics, and microbiota are key elements in this metabolic shift. Finally, we present a systemic model for understanding the complex etiology of neurodegeneration and how different regulatory systems are interconnected through a central metabolic pathway that becomes deregulated under specific conditions. |
| وصف الملف: | application/pdf |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6211aba6c74f38a545ac22bb245102e7Test https://doi.org/10.1038/s41598-020-72638-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6211aba6c74f38a545ac22bb245102e7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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