MULTIPLE SCLEROSIS, AUTOIMMUNITY AND METABOLISM
Despite decades of research on the molecular mechanisms and triggers of multiple sclerosis (MS), the pathogenesis and etiology of the disease has remained elusive.
The central hypothesis of this project is that multiple sclerosis (MS) arises as the consequence of a dysfunction of the metabolism of lipids. Specifically, the lipid metabolism of an MS patient is vulnerable due to genetic and/or environmental factors (such as lack of vitamin D, lack of sunlight, high fat/carbohydrate diet, etc.) that weakens critical nodes regulating metabolism, inflammation and the immune system. The regulatory functions of the weakened nodes collapse during an acute-phase inflammatory responses triggered by a pathogen (i.e. Epstein-Barr), trauma or stress. This collapse starts a feedback loop of increased oxidative stress, inflammatory response and proliferation of cytotoxic foam cells (oxidizing macrophages) that cross the blood brain barrier, catabolizing myelin and preventing remyelination.
IN COLLABORATION WITH:
- Dr. John Nieland, Aalborg University, Denmark
- Dr. Anne Mørkholt, Aalborg University, Denmark
- Dr. Michael Trabjerg, Aalborg University, Denmark
A. Corthals. (2011) Multiple Sclerosis is Not a Disease of the Immune System. The Quarterly Review of Biology, Vol. 86, No. 4 (December 2011), pp. 287-321, DOI: 10.1086/662453
Trabjerg MS, Mørkholt AS, Lichota J, Oklinski MKE, Andersen DC, Jønsson K, Mørk K, Skjønnemand MLN, Kroese LJ, Pritchard CEJ, Huijbers IJ, Gazerani P, Corthals A & John Dirk Vestergaard Nieland. (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. Nature Sci Rep 10, 15583 (2020). https://doi.org/10.1038/s41598-020-72638-8
Mørkholt AS, Oklinski MK, Larsen A, Bockermann R, Issazadeh-Navikas S, Nieland, JGK., Kwon, T-H, Corthals, A, Nielsen, S and J. Nieland. (2020) Pharmacological Inhibition of Carnitine Palmitoyl Transferase 1 Inhibits and Reverses Experimental Autoimmune Encephalitis in Rodents. PLOS ONE 15(6): e0234493. https://doi.org/10.1371/journal.pone.0234493
This project investigates the link between the metabolism of lipids, and the etiology of autoimmune disease, in particular multiple sclerosis (MS)