Search results for "Peroxysome"
showing 8 items of 8 documents
Activités cytotoxiques et pro-oxydantes d'acides gras à très longue chaîne sur des oligodendrocytes murins sauvages et déficients en Abcd1 et Acox1 :…
2010
X-ALD and P-NALD are two rare, peroxisomal metabolic and neurodegenerative diseases. ABCD1 and ACOX1 are known to be responsible for X-ALD and P-NALD, respectively. The actively demyelinating lesions in CNS, exhibited signs of oxidative stress and cell death. The accumulation of VLCFA in plasma and tissue is the biochemical common hallmark to both diseases. First, we characterized a murine oligodendrocytes cell line 158N to use it as a model. This 158N cell line which has characteristics of mature oligodendrocytes (expression of myelin proteins MOG, MBP, PLP), has also functional peroxisomes with Abcd1 and Acox1 proteins. Then, we studied the cytotoxic and pro-oxidative effects of VLCFA (C2…
Inactivation of peroxisomal ABC transporters, ABCD1 and ABCD2 in BV-2 microglial cells : Towards a better understanding of X-linked adrenoleukodystro…
2018
X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disorder characterized by very-long-chain fatty acid (VLCFA) accumulation resulting from a peroxisomal β-oxidation defect. The disease is caused by mutations in the ABCD1 gene, which encodes for a peroxisomal half ABC transporter predicted, like its closest homologue ABCD2, to participate in the entry of VLCFA-CoA into the peroxisome, the unique site of their β-oxidation. Progress in understanding the physiopathogenesis of X-ALD suffers from the lack of appropriate cell and animal models. Since peroxisomal defects in microglia seem to be a key element of the onset of the disease, we generated four microglial cell lines unab…
Involvment of docosanoïc acid (C22=0), and of very long chain fatty acids (tetracosanoïc acid (C24=0), hexacosanoïc acid (C26=0) in Alzheimer's disea…
2013
In the brain and in the plasma of patients with Alzheimer’s disease (AD), marked accumulation of C22:0 and of very long chain fatty acids (C24:0 ; C26:0) have been reported. Important decreases of docosahexaenoic acid (DHA; C22:6 n-3) have also been described as well as quantitative and qualitative modifications of plasmalogens. Altogether, these lipid modifications suggest an implication of peroxisomal metabolism disorders in the physiopathology of AD. Therefore, the biological activities of C22:0, C24:0 and C26:0 have been studied on human neuronal cells SK-N-BE. On these cells, the lipotoxicity of fatty acids (C22:0, C24:0 and C26:0) leads to various cellular modifications: topographical…
modifications peroxysomales associées à l'oxyapoptophagie induite par le 7-cétocholestérol et identification de lipides cytoprotecteurs
2020
Oxidative stress is often increased in several diseases such as age-related diseases (cardiovascular diseases, eye diseases (age-related macular degeneration (AMD) and cataracts), neurodegenerative diseases (Alzheimer's disease, multiple sclerosis), chronic inflammatory diseases (chronic inflammatory bowel disease (IBD)) as well as certain rare genetic diseases (Niemann Pick's disease, X-linked adrenoleukodystrophy (X-ALD)). Oxidative stress can oxidize various molecules, in particular the cholesterol present in lipid membranes, and lead to the formation of oxidized cholesterol derivatives: oxysterols. Some of them, such as 7-ketocholesterol (7KC), are toxic and may be the cause of a type o…
Étude des mécanismes moléculaires associés aux effets de l'ODN sur des cellules astrogliales et microgliales soumises à un stress oxydant : impact su…
2019
Neurodegenerative diseases are characterized by oxidative stress associated with mitochondrial damages leading to neuronal cell death. To mitigate these damages and promote neuronal cytoprotection and neurogenesis, endogenous (Neuropeptide: octadecaneuropeptide (ODN)) or exogenous (Polyphenols: resveratrol (RSV) and apigenin (API)) natural neurotrophic factors could be used as therapeutic agents to promote neuronal differentiation of immature and pluripotent stem cells. ODN is a peptide produced by astrocytes and known as a powerful neuroprotective agent. It is therefore of interest of studying its effects on the mobilization of calcium, its ability to protect neuronal cells against apoptos…
Molecular basis of the effects of argan oil on mitochondrial and peroxisomal metabolism of the fatty acids and inflammation
2012
The objective of this thesis work was to explore the molecular basis of Argan Oil (AO) effects on the mitochondrial and peroxisomal lipid metabolism and to elucidate its anti-inflammatory potential. We thus showed, initially, that the artisanal method preparation preserved the antioxidant properties of AO preventing the oxidation of the ferulic acid, by contrast to AO of commercial origin. Then, the treatment by the AO or lipopolysaccharides (LPS) of human fibroblasts, the cellular model of pseudo-neonatal adrenoleukodystrophy (P-NALD), revealed for the AO that peroxisomes proliferation is independent from the activation of the nuclear receptor PPARα and the co-activator PGC-1α. On the othe…
Etude structure/fonction du demi-transporteur ABCD2 dans le contexte de l'Adrénoleucodystrophie liée à l'X
2013
X-linked Adrenoleukodystrophy (X-ALD) is a rare neurodegenerative disease caused by deficiency of the peroxisomal half-transporter ABCD1, implicated in very long chain fatty acids import. Two additional half-transporters are located in the peroxisomal membrane: ABCD2 and ABCD3. Over-expression of ABCD2 is known to compensate for ABCD1 deficiency, making ABCD2 a therapeutic target for X-ALD treatment. In this context, the main objective of my thesis was to investigate the function and the structure of ABCD2, and more broadly, of peroxisomal ABC transporters.Half-transporters must at least dimerize to form a functional transporter. Alternative dimerization could modulate substrate specificity…
Altérations mitochondriales et processus inflammatoire dans la déficience en acyl- Coenzyme A oxydase 1 peroxysomale
2012
Acyl-CoA oxidase 1 (ACOX1) is the rate-limiting enzyme of the peroxisomal fatty acid β-oxidation pathway of very-long-chain fatty acid (VLCFAs). In humans, ACOX1 deficiency, also called pseudo-neonatal adrenoleukodystrophy, is an autosomal recessive and a severe form of the peroxisomal β-oxidation deficiency. Patients suffer from severe delayed motor development followed by a progressive neurological regression including progressive hypodensity of cerebral white matter, hepatomegaly and deafness and die during late-infantile period. Elevated plasma and tissues VLCFAs levels are detected in these patients. Mice lacking ACOX1 develop severe microvesicular steatohepatitis with increased intrah…