Neurodegeneration in multiple sclerosis: The role of oxidative stress and excitotoxicity

Gonsette, R

doi:10.1016/j.jns.2008.06.029

Cited by 242 publications

(182 citation statements)

References 83 publications

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“…There are three main types of MS, defined as: relapsing-remitting (RR), secondary progressive (SP) and primaryprogressive (PP) with progressive-relapsing (PR) recently distinguished as an additional subtype [31,32]. There is evidence that MS is characterized not only by immune mediated inflammatory reactions but also by neurodegenerative processes [33,34]. A variety of studies, supporting a role for oxidative stress in MS, indicate that endogenous antioxidants are decreased in MS, and damage to mitochondria induced by lipid peroxidation can lead to further ROS generation [35][36][37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Redox regulation of cellular stress response in multiple sclerosis

Pennisi

Cornelius

Cavallaro

et al. 2011

Biochemical Pharmacology

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Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease with characteristic foci of inflammatory demyelination in the brain, spinal cord, and optic nerves. Recent studies have demonstrated not only that axonal damage and neuronal loss are significant pathologic components of MS, but that this neuronal damage is thought to cause the permanent neurologic disability often seen in MS patients. Emerging finding suggests that altered redox homeostasis and increased oxidative stress, primarily implicated in the pathogenesis of MS, are a trigger for activation of a brain stress response. Relevant to maintenance of redox homeostasis, integrated mechanisms controlled by vitagenes operate in brain in preserving neuronal survival during stressful conditions. Vitagenes encode for heat shock proteins (Hsp) Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. In the present study we assess stress response mechanisms in the CSF, plasma and lymphocytes of control patients compared to MS patients. We found that the levels of vitagenes Hsp72, Hsc70, HO-1, as well as oxidative stress markers carbonyls and hydroxynonenals were significantly higher in the blood and CSF of MS patients than in control patients. In addition, an increased expression of Trx and sirtuin 1, together with a decrease in the expression of TrxR were observed. Our data strongly support a pivotal role for redox homeostasis disruption in the pathogenesis of MS and, consistently with the notion that new therapies that prevent neurodegeneration through nonimmunomodulatory mechanisms can have a tremendous potential to work synergistically with current MS therapies, unravel important targets for new cytoprotective strategies

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Section: Discussionmentioning

confidence: 99%

Redox regulation of cellular stress response in multiple sclerosis

Pennisi

Cornelius

Cavallaro

et al. 2011

Biochemical Pharmacology

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“…The activated microglia/macrophages initiate the MS by the generation of ROS [121] that can induce lipid peroxidation, results in the demylination and damage of neurons. Elevated TBARS levels and reduced protein SH groups, the representatives of protein oxidation and slightly reduced SOD was reported in MS patients [122].…”

Section: Multiple Sclerosis (Ms)mentioning

confidence: 99%

Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases

2014

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Free radicals and other oxidants have gained importance in the field of biology due to their central role in various physiological conditions as well as their implication in a diverse range of diseases. The free radicals, both the reactive oxygen species (ROS) and reactive nitrogen species (RNS), are derived from both endogenous sources (mitochondria, peroxisomes, endoplasmic reticulum, phagocytic cells etc.) and exogenous sources (pollution, alcohol, tobacco smoke, heavy metals, transition metals,

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“…Reactive oxygen species may contribute to CNS injury and MS lesion formation (Gonsette, 2008). NQO1 protects cells from oxidative injury by maintaining antioxidative forms of vitamin E and ubiquinone and is upregulated in MS lesions (van Horssen et al, 2006).…”

Section: Nad(p)h: Quinone Reductase 1 (Nqo1)mentioning

confidence: 99%

Genetics of primary progressive multiple sclerosis

Cree

2014

Handbook of Clinical Neurology

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Neurodegeneration in multiple sclerosis: The role of oxidative stress and excitotoxicity

Cited by 242 publications

References 83 publications

Redox regulation of cellular stress response in multiple sclerosis

Redox regulation of cellular stress response in multiple sclerosis

Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases

Genetics of primary progressive multiple sclerosis

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