The Role of Oxidative Stress in Amyotrophic Lateral Sclerosis and Parkinson’s Disease

Baillet, Athan; Chanteperdrix, Vanessa; Trocmé, Candice; Casez, Pierre; Garrel, Catherine; Besson, Gérard

doi:10.1007/s11064-010-0212-5

Cited by 128 publications

(92 citation statements)

References 49 publications

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“…Enhancement of DOPAL auto-oxidation is highly relevant given that SOD is up-regulated in the substantia nigra of PD patients (48,49). Superoxide dismutation may be beneficial for cells but also result in the deleterious consequence of increased formation of DOPAL radicals and quinones.…”

Section: Discussionmentioning

confidence: 99%

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

Anderson

Mariappan

Buettner

et al. 2011

Journal of Biological Chemistry

122

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The oxidation and toxicity of dopamine is believed to contribute to the selective neurodegeneration associated with Parkinson disease. The formation of reactive radicals and quinones greatly contributes to dopaminergic toxicity through a variety of mechanisms. The physiological metabolism of dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL) via monoamine oxidase significantly increases its toxicity. To more adequately explain this enhanced toxicity, we hypothesized that DOPAL is capable of forming radical and quinone species upon oxidation. Here, two unique oxidation products of DOPAL are identified. Several different oxidation methods gave rise to a transient DOPAL semiquinone radical, which was characterized by electron paramagnetic resonance spectroscopy. NMR identified the second oxidation product of DOPAL as the ortho-quinone. Also, carbonyl hydration of DOPAL in aqueous media was evident via NMR. Interestingly, the DOPAL quinone exists exclusively in the hydrated form. Furthermore, the enzymatic and chemical oxidation of DOPAL greatly enhance protein cross-linking, whereas auto-oxidation results in the production of superoxide. Also, DOPAL was shown to be susceptible to oxidation by cyclooxygenase-2 (COX-2). The involvement of this physiologically relevant enzyme in both oxidative stress and Parkinson disease underscores the potential importance of DOPAL in the pathogenesis of this condition. Parkinson disease (PD)2 involves specific loss of dopaminergic nuclei in the substantia nigra of the brain (1). Although the exact causes of this selective degeneration are unknown (2), the role of affected cells as centers of dopamine (DA) synthesis, storage, and metabolism suggests that DA may be an endogenous neurotoxin (3, 4) that contributes to the pathogenesis of PD. DA may act as a source of cellular oxidative stress and is known to undergo oxidation (Scheme 1) to cytotoxic radicals and quinones (5-8). Such oxidations can occur spontaneously or via metal-or enzyme-catalyzed mechanisms (9). One-electron oxidation of DA produces a radical capable of interfering with DA storage and causing oxidative protein and DNA modifications (5, 6, 10). Similarly, two-electron oxidation of DA to an ortho-quinone results in reactivity with cellular nucleophiles such as thiols and proteins (8, 11). Both species are capable of redox cycling, which could deplete cellular oxidative defenses. Also, in the presence of transition metals and/or O 2 , such oxidations could result in the production of ROS capable of inducing lipid peroxidation and damage to other cellular macromolecules (12). Another potential mechanism of toxicity for DA is its physiological metabolism to 3,4-dihydroxyphenylacetaldehyde (DOPAL) (13).DOPAL is a very reactive aldehyde that is 100 -1000-fold more toxic than DA both in vivo and in vitro (14,15). Physiological levels of DOPAL in the substantia nigra are ϳ2 M; levels as low as 6 M can exert significant toxicity (16). Reactivity with proteins, presumably via Schiff base formation, is an important mechanism o...

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Section: Discussionmentioning

confidence: 99%

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

Anderson

Mariappan

Buettner

et al. 2011

Journal of Biological Chemistry

122

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“…Catalase is reported to decrease lipid peroxidation products (87) Under OS conditions, as demonstrated in AD, PD, and ALS (25), catalase activity is lowered significantly, thereby reducing antioxidant potential (104).…”

Section: Catalasementioning

confidence: 99%

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

157

142

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Several studies demonstrated that oxidative damage is a characteristic feature of many neurodegenerative diseases. The accumulation of oxidatively modified proteins may disrupt cellular functions by affecting protein expression, protein turnover, cell signaling, and induction of apoptosis and necrosis, suggesting that protein oxidation could have both physiological and pathological significance. For nearly two decades, our laboratory focused particular attention on studying oxidative damage of proteins and how their chemical modifications induced by reactive oxygen species/reactive nitrogen species correlate with pathology, biochemical alterations, and clinical presentations of Alzheimer's disease. This comprehensive article outlines basic knowledge of oxidative modification of proteins and lipids, followed by the principles of redox proteomics analysis, which also involve recent advances of mass spectrometry technology, and its application to selected age-related neurodegenerative diseases. Redox proteomics results obtained in different diseases and animal models thereof may provide new insights into the main mechanisms involved in the pathogenesis and progression of oxidativestress-related neurodegenerative disorders. Redox proteomics can be considered a multifaceted approach that has the potential to provide insights into the molecular mechanisms of a disease, to find disease markers, as well as to identify potential targets for drug therapy. Considering the importance of a better understanding of the cause/effect of protein dysfunction in the pathogenesis and progression of neurodegenerative disorders, this article provides an overview of the intrinsic power of the redox proteomics approach together with the most significant results obtained by our laboratory and others during almost 10 years of research on neurodegenerative disorders since we initiated the field of redox proteomics. Antioxid. Redox Signal. 17, 1610-1655.

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“…Role of oxidative stress in toxin-induced Parkinsonism could not be ignored [4,22]. Owing to high oxygen consumption, elevated level of unsaturated fatty acids and low level of antioxidants, the brain is found to be more vulnerable to free radicals [12].…”

Section: Introductionmentioning

confidence: 99%

Cypermethrin alters the status of oxidative stress in the peripheral blood: relevance to Parkinsonism

et al. 2014

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Parkinson's disease (PD) is a motor scarcity disorder characterized by the striatal dopamine deficiency owing to the selective degeneration of the nigrostriatal dopaminergic neurons. While oxidative stress is implicated in PD, prolonged exposure to moderate dose of cypermethrin induces Parkinsonism. The study aimed to investigate the status of oxidative stress indicators and antioxidant defence system of the polymorphonuclear leukocytes (PMNs), platelets and plasma to delineate the effect of Parkinsonian dose of cypermethrin in the peripheral blood of rats and its subsequent relevance to Parkinsonism. Nitrite content, lipid peroxidation (LPO) and activity of superoxide dismutase (SOD), catalase, glutathione reductase (GR) and glutathione-S-transferase (GST) were measured in the PMNs, platelets and plasma of control and cypermethrin-treated rats in the presence or absence of a microglial activation inhibitor, minocycline or a dopamine precursor containing the peripheral 3,4-dihydroxyphenylalanine decarboxylase inhibitor, named syndopa, employing the standard procedures. The striatal dopamine was measured to assess the degree of neurodegeneration/neuroprotection. Cypermethrin increased nitrite and LPO in the plasma, platelets and PMNs while it reduced the striatal dopamine content. Catalase and GST activity were increased in the PMNs and platelets; however, it was reduced in the plasma. Conversely, SOD and GR activities were reduced in the PMNs and platelets but increased in the plasma. Minocycline or syndopa reduced the cypermethrin-mediated changes towards normalcy. The results demonstrate that cypermethrin alters the status of oxidative stress indicators and impairs antioxidant defence system of the peripheral blood, which could be effectively salvaged by minocycline or syndopa. The results could be of value for predicting the nigrostriatal toxicity relevant to Parkinsonism.

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The Role of Oxidative Stress in Amyotrophic Lateral Sclerosis and Parkinson’s Disease

Cited by 128 publications

References 49 publications

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

Oxidation of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopaminergic Metabolite, to a Semiquinone Radical and an ortho-Quinone

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Cypermethrin alters the status of oxidative stress in the peripheral blood: relevance to Parkinsonism

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