Isoprenoid biosynthesis in multiple sclerosis

Steen, Göran O.; Axelsson, Hans; Bowallius, Magnus; Holthuis, Nicholas; Molander, Britt-Marie

doi:10.1111/j.1600-0404.1985.tb00879.x

Cited by 8 publications

(4 citation statements)

References 13 publications

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“…Thus, potential inhibition of PARP-1 by increased levels of 2-PY could be both implicated at early steps and later on, as a potential compensatory mechanism. Concerning ubiquinone, previous data suggested an impairment in ubiquinone biosynthesis in MS (Steen et al 1985;Syburra and Passi 1999), although later data in serum suggested that ubiquinone levels could not be used as a risk nor prognosis factor in the follow up of MS (de Bustos et al 2000). Interestingly, it has been detected that the antioxidant protein NAD(P)H:quinone oxidoreductase 1 (NQO1), whose activity is dependent on ubiquinone levels, is strongly upregulated in MS lesions, specially in pathological astrocytes and activated macrophages (Horssen et al 2006).…”

Section: Discussionmentioning

confidence: 95%

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Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism

Gonzalo

Brieva

Tatzber

et al. 2012

Journal of Neurochemistry

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Metabolomic and lipidomic analyses have been used for the profiling of neurodegenerative processes, both in targeted and untargeted approaches. In this work we have applied these techniques to the study of CSF samples of multiple sclerosis (MS) patients (n = 9), compared with samples of non-MS individuals (n = 9) using mass-spectrometry. We have used western-blot and analyzed cell culture to confirm pathogenic pathways suggested by mass-spectrometric measurements. The results of the untargeted approach of metabolomics and lipidomics suggest the existence of several metabolites and lipids discriminating both populations. Applying targeted lipidomic analyses focused to a pathogenic pathway in MS, oxidative stress, reveal that the lipid peroxidation marker 8-isoprostaglandin F2a is increased in CSF from MS patients. Furthermore, as lipid peroxidation exerts its pathogenical effects through protein modification, we studied the incidence of protein lipoxidation, revealing specific increases in carboxymethylated, neuroketal and malondialdehyde-mediated protein modifications in proteins of CSF from MS patients, despite the absence of their precursors glyoxal and methylglyoxal. Finally, we report that the level of neuroketal-modified proteins correlated with a hitherto unknown increased amount of autoantibodies against lipid peroxidation-modified proteins in CSF, without compensation by signaling induced by lipid peroxidation via peroxisome proliferator-activated receptor c (PPARc). The results, despite the limitation of being obtained in a small population, strongly suggest that autoimmunity against in situ produced epitopes derived from lipid peroxidation can be a relevant pathogenic factor in MS. Keywords: autoimmunity, lipid peroxidation, PPAR, protein oxidation. J. Neurochem. (2012) 123, 622-634. Multiple sclerosis is a complex pathology belonging to the group of chronic inflammatory autoimmune diseases. Several risk factors have been defined for this disease such as genetic pre-disposition, dietary and other environmental factors such as obesity and smoking habit (recently reviewed in (Young 2011). Patients suffering from this disease have a spectrum of clinical manifestations, generally episodic, with frequent intervals of exacerbations followed by periods of remission.The ethiopathogeny of this disease comprises many aspects of immune system with dysfunctionality, including dearranged cytokine profile, T-cell population imbalance, abnormal presence of altered B cell and inmunoglobins in CNS, inappropriate activation of natural killer, dendritic cells and Received March 6, 2012; revised manuscript received August 18, 2012; accepted August 19, 2012. Address correspondence and reprint requests to Dr Manuel Portero-Otin, Universidad de Lleida c/Montserrat Roig 2, 25008 Lleida, Spain. E-mail: manuel.portero@mex.udl.catAbbreviations used: 2-PY, N1-methyl-2-pyridone-5-carboxamide; 8-iso-PGF2a, 8-iso-prostaglandin F2a; CML, carboxymethyl-lysine; HODE, hydroxyoctadecadienoic acid; LC, liquid chromatography;...

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Section: Discussionmentioning

confidence: 95%

“…Concerning ubiquinone, previous data suggested an impairment in ubiquinone biosynthesis in MS (Steen et al . ; Syburra and Passi ), although later data in serum suggested that ubiquinone levels could not be used as a risk nor prognosis factor in the follow up of MS (de Bustos et al . ).…”

Section: Resultsmentioning

confidence: 99%

Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism

Gonzalo

Brieva

Tatzber

et al. 2012

Journal of Neurochemistry

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“…With regard to CoQ10 deficiency in MS, Gironi et al [41] reported reduced blood levels of CoQ10 (mean value 0.48 µg/mL versus 0.62 µg/mL for normal controls) in a series of 87 patients with MS. Similarly, Steen et al [42] found serum CoQ10 levels to be significantly reduced (mean value of 0.54 µg/mL versus 0.84 µg/mL for normal controls) in a set of 20 MS patients. In contrast to the above studies, de Bustos et al [43] found no significant difference in serum CoQ10 levels between MS patients and normal controls.…”

Section: Autoimmune Neuromuscular and Musculoskeletal Disordersmentioning

confidence: 77%

Coenzyme Q10 and Autoimmune Disorders: An Overview

Mantle,

Hargreaves

2024

IJMS

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Some 90 autoimmune disorders have been described in medical literature, affecting most of the tissues within the body. Autoimmune disorders may be difficult to treat, and there is a need to develop novel therapeutic strategies for these disorders. Autoimmune disorders are characterised by mitochondrial dysfunction, oxidative stress, and inflammation; there is therefore a rationale for a role for coenzyme Q10 in the management of these disorders, on the basis of its key role in normal mitochondrial function, as an antioxidant, and as an anti-inflammatory agent. In this article, we have therefore reviewed the potential role of CoQ10, in terms of both deficiency and/or supplementation, in a range of autoimmune disorders.

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“…Hildebrandt acid [VIII] and GA [III] are excreted in urine as compounds that monitor bioexposure to geraniol [I] and citral [II] as environmental substances, but considering that geraniol [I] is an endogenous metabolite, these two organic acids may be physiological metabolites ( 7 ). Popjak's group has shown that dimethylallyl diphosphate (DMAPP: C 5 ), geranyl diphosphate (C 10 ), and farnesyl diphosphate (FPP: C 15 ), diphosphate intermediates from mevalonic acid (MVA) to squalene, which are important intermediates in cholesterol synthesis, are all enzymatically dephosphorylated to dimethylallyl alcohol, geraniol [I], and farnesol, respectively.…”

Section: Hildebrandt Acidmentioning

confidence: 99%

Geranylgeranoic acid, a bioactive and endogenous fatty acid in mammals: a review

Shidoji

2023

Journal of Lipid Research

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Isoprenoid biosynthesis in multiple sclerosis

Cited by 8 publications

References 13 publications

Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism

Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism

Coenzyme Q10 and Autoimmune Disorders: An Overview

Geranylgeranoic acid, a bioactive and endogenous fatty acid in mammals: a review

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