Thomas Nury, Aline Yammine, Franck Menetrier, Amira Zarrouk, Anne Vejux, Gérard Lizard
Abstract
["Peroxisomopathies are qualitative or quantitative deficiencies in peroxisomes which lead to increases in the level of very-long-chain fatty acids (VLCFA) and can be associated with more or less pronounced dysfunction of central nervous system cells: glial and microglial cells. Currently, in frequent neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS), peroxisomal dysfunction is also suspected due to an increase in VLCFA, which can be associated with a decrease of plasmalogens, in these patients. Moreover, in patients suffering from peroxisomopathies, such as X-linked adrenoleukodystrophy (X-ALD), AD, or MS, the increase in oxidative stress observed leads to the formation of cytotoxic oxysterols: 7-ketocholesterol (7KC) and 7\u03b2-hydroxycholesterol (7\u03b2-OHC). These observations led to the demonstration that 7KC and 7\u03b2-OHC alter the biogenesis and activity of peroxisomes in glial and microglial cells. In X-ALD, AD, and MS, it is suggested that 7KC and 7\u03b2-OHC\u00a0affecting the peroxisome, and which also induce mitochondrial dysfunctions, oxidative stress, and inflammation, could promote neurodegeneration. Consequently, the study of oxisome in peroxisomopathies, AD and MS, could help to better understand the pathophysiology of these diseases to identify therapeutic targets for effective treatments."]
Address:
Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/University of Bourgogne Franche-Comté/Inserm, Dijon, France.; Laboratory 'Bioactive Molecules', Faculty of Sciences-2, Doctoral School of Sciences and Technologie, University Libanese, Jdeidet, Lebanon.; University of Bourgogne-Franche Comté, CNRS, INRA, 'Centre des Sciences du Goût et de l'Alimentation (CSGA)', Dijon, France.; Faculty of Medicine, Laboratory 'Nutrition, Functional Food and Vascular Health', UR12ES05, University of Monastir, Monastir, Tunisia.; Faculty of Medicine, University of Sousse, Laboratory of Biochemistry, Sousse, Tunisia.; Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/University of Bourgogne Franche-Comté/Inserm, Dijon, France.
[email protected].; Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/University of Bourgogne Franche-Comté/Inserm, Dijon, France.
[email protected].