Role of Oxidative Stress in the Progression of Alzheimer's Disease

Sultana, Rukhsana; Butterfield, D. Allan

doi:10.3233/jad-2010-1222

Cited by 284 publications

(211 citation statements)

References 129 publications

(204 reference statements)

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“…AD is the most prevalent form of human dementia, with a frequency that progressively increases in aging societies (10). A pivotal role in development and progression of late-onset AD, and other age-dependent dementias, has been attributed to inflammatory and oxidative stress cascades in the brain (11,12), which are potentiated by elevated levels of nitrosating and oxidizing species (13,14).…”

mentioning

confidence: 99%

S -nitrosation of proteins relevant to Alzheimer’s disease during early stages of neurodegeneration

Seneviratne

Nott

Bhat

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Protein S-nitrosation (SNO-protein), the nitric oxide-mediated posttranslational modification of cysteine thiols, is an important regulatory mechanism of protein function in both physiological and pathological pathways. A key first step toward elucidating the mechanism by which S-nitrosation modulates a protein's function is identification of the targeted cysteine residues. Here, we present a strategy for the simultaneous identification of SNO-cysteine sites and their cognate proteins to profile the brain of the CK-p25-inducible mouse model of Alzheimer's disease-like neurodegeneration. The approach-SNOTRAP (SNO trapping by triaryl phosphine)-is a direct tagging strategy that uses phosphine-based chemical probes, allowing enrichment of SNO-peptides and their identification by liquid chromatography tandem mass spectrometry. SNOTRAP identified 313 endogenous SNO-sites in 251 proteins in the mouse brain, of which 135 SNO-proteins were detected only during neurodegeneration. S-nitrosation in the brain shows regional differences and becomes elevated during early stages of neurodegeneration in the CK-p25 mouse. The SNO-proteome during early neurodegeneration identified increased S-nitrosation of proteins important for synapse function, metabolism, and Alzheimer's disease pathology. In the latter case, proteins related to amyloid precursor protein processing and secretion are S-nitrosated, correlating with increased amyloid formation. Sequence analysis of SNO-cysteine sites identified potential linear motifs that are altered under pathological conditions. Collectively, SNOTRAP is a direct tagging tool for global elucidation of the SNO-proteome, providing functional insights of endogenous SNO proteins in the brain and its dysregulation during neurodegeneration.S-nitrosation | Alzheimer's disease | secretase pathway | presenilin pathway | neurodegeneration P rotein S-nitrosation (SNO-protein), in which a cysteine (Cys) thiol is converted to a nitrosothiol (RSNO), is an important posttranslational modification (PTM). Cys residues targeted for S-nitrosation often impact enzyme activity, protein localization, and protein-protein interactions (1). SNO begins with the production of nitric oxide radicals (NO • ) via conversion of L-arginine to L-citrulline by nitric oxide synthase 1 (NOS1) (neuronal), NOS2 (inducible), and NOS3 (endothelial). NO-mediated SNO PTMs are thought to occur in vivo predominantly through radical recombination between NO • and a thiyl radical, transnitrosation by low-molecular weight NO carriers such as S-nitrosoglutathione (GSNO), or protein-assisted transnitrosation (2-8). In the healthy brain, low levels of NO and normal SNO PTMs play important roles in regulating synaptic plasticity, gene expression, and neuronal survival. In contrast, elevated NO levels associated with aging and environmental stress have been linked to neurological pathologies, including Alzheimer's (AD), Parkinson's, and Huntington's disease (9). AD is the most prevalent form of human dementia, with a frequency that progressiv...

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mentioning

confidence: 99%

S -nitrosation of proteins relevant to Alzheimer’s disease during early stages of neurodegeneration

Seneviratne

Nott

Bhat

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…There is consistent evidence in literature showing the involvement of free radical-induced oxidative damage in the etiopathogenesis of AD, since oxidative stress is one of the earliest events in AD pathogenesis [18,[80][81][82]. Moreover, oxidative damage has been shown in the blood, CSF and brain of neurological patients with probable AD [83][84][85].…”

Section: Involvement Of Sam In Oxidative Stress and Neurodegenerationmentioning

confidence: 51%

“…Normal functioning of this metabolic cycle is essential for growth and development and impairment of this metabolism; transmethylation efficiency is associated with many diseases like cardiovascular diseases [4][5], liver diseases [6][7][8][9], neural tube defects [10] and brain diseases [11][12][13][14][15][16]. One-carbon metabolism alterations, low methylation and oxidative stress are all linked to Late Onset Alzheimer's Disease (LOAD) [17][18][19][20][21][22][23][24] Moreover, wide confirmed reports underline the role of SAM dependent reactions in age related neurodegeneration also showing the role of SAM supplementation in restoring one-carbon metabolism alterations, particularly in neurodegenerative diseases [25][26][27][28][29]. SAM is currently marketed as a nutritional supplement worldwide, whereas it is sold as a prescription drug in several countries of the European Union.…”

Section: Introductionmentioning

confidence: 99%

Role of S-adenosylmethionine in the Modulation of Oxidative Stress- Related Neurodegeneration

Cavallaro¹,

Fuso²,

D’Erme³

et al. 2016

Int J Clin Nutr Diet

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S-adenosyl-L-methionine (SAM) is the main biological methyl donor in transmethylation reactions, consisting in the transferring of a methyl moiety to different substrates including DNA, proteins, lipids and RNA. SAM level in the organism decreases with aging and restoring the original levels through exogenous supplementation is an important tool for the improvement of many vital functions. Indeed, SAM deficiency may contribute to the onset of several diseases, i.e. depression, liver diseases, osteoarthritis and senile neurological disorders such as Alzheimer's and Parkinson's diseases. Recent evidences indicate that SAM may have an involvement in oxidative stress, a process which typically involves an alteration of cellular sulfur amino acids homeostasis. SAM is not only the principal methyl donor, but also a precursor of glutathione, the major endogenous antioxidant, whose role in counteracting oxidative stress is well known. In this review we will highlight the role of SAM not just as a methyl-donor but also as a regulator of different metabolic pathways involved in the antioxidant response in brain related disorders. Role of S-adenosylmethionine in the Modulation of Oxidative StressRelated Neurodegeneration Review ArticleOpen Access IntroductionThe interaction between environmental and genetic factors plays a fundamental role in inducing and modulating the aging processes towards brain disorders. Among environmental factors, diet and nutritional lifestyle have a key role in brain health through the alteration of the intake or the bioavailability of metabolites and cofactors. Specific nutritional factors have particular impact on one-carbon metabolism, which is a complex biochemical pathway regulated by the presence of folate, vitamin B12 and B6 (among other metabolites) and leading to the production of S-adenosyl-L-methionine (SAM), the main biological methyl donor in transmethylation reactions, consisting in the transferring of a methyl moiety to different substrates including DNA, proteins, lipids and RNA. This metabolism involves three interrelated biochemical pathways: folate cycle, transsulfuration pathway and methionine cycle. These three metabolic sequences were first combined and correlated in 1964 by Laster's group [1][2][3] giving the integrated point of view of transmethylation and transsulfuration pathways, linking sulfur amino acid metabolism to the provision of methyl groups for many biochemical processes. Normal functioning of this metabolic cycle is essential for growth and development and impairment of this metabolism; transmethylation efficiency is associated with many diseases like cardiovascular diseases [4][5], liver diseases [6-9], neural tube defects [10] and brain diseases [11][12][13][14][15][16]. One-carbon metabolism alterations, low methylation and oxidative stress are all linked to Late Onset Alzheimer's Disease (LOAD) [17][18][19][20][21][22][23][24] Moreover, wide confirmed reports underline the role of SAM dependent reactions in age related neurodegeneration also showi...

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“…Much evidence supported that free radical induced oxidative damage may play a role in the pathogenesis of AD (30,31). Features of brain, including a high content of readily oxidized fatty acids, high use of oxygen, and low levels of antioxidants, make it especially sensitive to oxidative damage.…”

Section: Free Radical Oxidative Damagementioning

confidence: 99%

“…Studies found that puerarin had potent effects in improving learning and memory disorders induced by scopolamine or D-galactose in a mouse model (65). Yan et al reported that puerarin protected neurons against apoptosis in the cortex and hippocampus of AD rats caused by Aβ [25][26][27][28][29][30][31][32][33][34][35] through downregulating Aβ and Bax expression in brain tissues, therefore alleviating the spatial learning and memory impairment of diseased animals (66). The anti-AD effects of puerarin were also suggested to be related to its abilities in decreasing the lipid peroxidase levels and increasing superoxide dismutase levels in brain tissues, enhancing cerebral blood flow, and improving brain microcirculation (67,68).…”

Section: Puerarinmentioning

confidence: 99%

Research progresses on flavonoids isolated from traditional Chinese medicine in treatment of Alzheimer's disease

Gao

Inagaki

Liu

2013

Intractable Rare Dis Res

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Role of Oxidative Stress in the Progression of Alzheimer's Disease

Cited by 284 publications

References 129 publications

S -nitrosation of proteins relevant to Alzheimer’s disease during early stages of neurodegeneration

S -nitrosation of proteins relevant to Alzheimer’s disease during early stages of neurodegeneration

Role of S-adenosylmethionine in the Modulation of Oxidative Stress- Related Neurodegeneration

Research progresses on flavonoids isolated from traditional Chinese medicine in treatment of Alzheimer's disease

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