7-Ketocholesterol- and 7β-Hydroxycholesterol-Induced Peroxisomal Disorders in Glial, Microglial and Neuronal Cells: Potential Role in Neurodegeneration : 7-ketocholesterol and 7β-hydroxycholesterol-Induced Peroxisomal Disorders and Neurodegeneration.
Fiche publication
Date publication
janvier 2020
Journal
Advances in experimental medicine and biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr LIZARD Gérard
Tous les auteurs :
Nury T, Yammine A, Menetrier F, Zarrouk A, Vejux A, Lizard G
Lien Pubmed
Résumé
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 7β-hydroxycholesterol (7β-OHC). These observations led to the demonstration that 7KC and 7β-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 7β-OHC affecting 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.
Mots clés
7-ketocholesterol, 7β-hydroxycholesterol, Alzheimer’s disease, Multiple sclerosis, Oxysterol, Peroxisome, Very-long-chain fatty acids, X-linked adrenoleukodystrophy
Référence
Adv Exp Med Biol. 2020 ;1299:31-41