Protective effects of S-nitrosoglutathione against amyloid β-peptide neurotoxicity

Ju, Tz-Chuen; Chen, Shang-Der; Liu, Chia Chin; Yang, Ding

doi:10.1016/j.freeradbiomed.2004.12.019

Cited by 91 publications

(58 citation statements)

References 47 publications

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“…37 and 38). Moreover, antioxidants have been used as a therapeutic approach to treat AD (39,40), but have been only mildly effective, perhaps because they are not sufficiently robust or because of their nonspecific nature or incorrect timing of administration. Our studies show that a mitochondria-targeted antioxidant such as a SOD-2 mimetic could offer potentially better therapeutic outcomes in the treatment of AD.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease

Massaad

Washington

Pautler

et al. 2009

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

200

143

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Alzheimer's disease (AD) is a neurodegenerative disease characterized by impaired cognitive function and the deposition of extracellular amyloid plaques and intracellular tangles. Although the proximal cause of AD is not well understood, it is clear that amyloid-␤ (A␤) plays a critical role in AD pathology. Recent studies also implicate mitochondrial abnormalities in AD. We investigated this idea by crossing mice that overexpress mitochondrial superoxide dismutase (SOD-2) with the Tg2576 mouse model of AD that overexpresses the human amyloid precursor protein carrying the Swedish mutation (K670N:M671L). We found that overexpression of SOD-2 decreased hippocampal superoxide, prevented AD-related learning and memory deficits, and reduced A␤ plaques. Interestingly, SOD-2 overexpression did not affect the absolute levels of A␤1-40 and A␤1-42, but did significantly reduce the A␤1-42 to A␤1-40 ratio, thereby shifting the balance toward a less amyloidogenic A␤ composition. These findings directly link mitochondrial superoxide to AD pathology and demonstrate the beneficial effects of a mitochondrial anti-oxidant enzyme, hence offering significant therapeutic implications for AD.antioxidant ͉ dementia ͉ mitochondria ͉ oxidative stress ͉ reactive oxygen species

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Section: Discussionmentioning

confidence: 99%

Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease

Massaad

Washington

Pautler

et al. 2009

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

200

143

View full text Add to dashboard Cite

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“…In fact, Trx eliminates singlet oxygen, hydroxyl radical and hydrogen peroxide [90]. It has also been reported that some of the neuroprotective effects of GSNO on beta-amyloid-or ferrous citrate-induced toxicity in rat cortical neurons or in rat substantia nigra can be due to the activation of multiple signalling pathways including thioredoxin [91,92]. Interestingly, the interaction between Trx and GSNO seems to involve both the activation of sGC and the following cGMP generation and a direct S-nitrosylation reaction [92].…”

Section: Heat Shock Protein 70mentioning

confidence: 99%

Cellular Stress Response: A Novel Target for Chemoprevention and Nutritional Neuroprotection in Aging, Neurodegenerative Disorders and Longevity

Calabrese

Cornelius

Mancuso³

et al. 2008

Neurochem Res

256

227

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The predominant molecular symptom of aging is the accumulation of altered gene products. Moreover, several conditions including protein, lipid or glucose oxidation disrupt redox homeostasis and lead to accumulation of unfolded or misfolded proteins in the aging brain. Alzheimer's and Parkinson's diseases or Friedreich ataxia are neurological diseases sharing, as a common denominator, production of abnormal proteins, mitochondrial dysfunction and oxidative stress, which contribute to the pathogenesis of these so called "protein conformational diseases". The central nervous system has evolved the conserved mechanism of unfolded protein response to cope with the accumulation of misfolded proteins. As one of the main intracellular redox systems involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins (Hsp) Hsp70 and heme oxygenase-1, as well as thioredoxin reductase and sirtuins. Nutritional studies show that ageing in animals can be significantly influenced by dietary restriction. Thus, the impact of dietary factors on health and longevity is an increasingly appreciated area of research. Reducing energy intake by controlled caloric restriction or intermittent fasting increases lifespan and protects various tissues against disease. Genetics has revealed that ageing may be controlled by changes in intracellular NAD/NADH ratio regulating sirtuin, a group of proteins linked to aging, metabolism and stress tolerance in several organisms. Recent findings suggest that several phytochemicals exhibit biphasic dose responses on cells with low doses activating signaling pathways that result in increased expression of vitagenes encoding survival proteins, as in the case of the Keap1/Nrf2/ARE pathway activated by curcumin and NAD/NADH-sirtuin-1 activated by resveratrol. Consistently, the neuroprotective roles of dietary antioxidants including curcumin, acetyl-L-carnitine and carnosine have been demonstrated through the activation of these redox-sensitive intracellular pathways. Although the notion that stress proteins are neuroprotective is broadly accepted, still much work needs to be done in order to associate neuroprotection with specific pattern of stress responses. In this review the importance of vitagenes in the cellular stress response and the potential use of dietary antioxidants in the prevention and treatment of neurodegenerative disorders is discussed.

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“…In vitro, Aβ has been shown to induce apoptosis via the sphingomyelin/ceramide pathway in various brain cells, including human and rat primary neurons (Jana and Pahan, 2004;Ju et al, 2005;Malaplate-Armand et al, 2006), rat oligodendrocytes (Cheng et al, 2003;Lee et al, 2004;Malaplate-Armand et al, 2006;Zeng et al, 2005), rat astrocytes and glial cells (Ayasolla et al, 2004), and murine neuroblastoma cells (Satoi et al, 2005). Calcium-dependent phospholipase A (cPLA) (Malaplate-Armand et al, 2006), inducible nitric oxide synthase (iNOS) (Ayasolla et al, 2004;Zeng et al, 2005), the p75 neurotrophin receptor (p75NTR) (Costantini et al, 2005), and NADPH oxidase (Jana and Pahan, 2004) have each been shown to be involved in the Aβ-related activation of the sphingomyelin/ceramide pathway.…”

Section: Introductionmentioning

confidence: 99%

Deregulation of sphingolipid metabolism in Alzheimer's disease

Huang²,

Li³

et al. 2010

Neurobiology of Aging

450

468

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Abnormal sphingolipid metabolism has been previously reported in Alzheimer's disease (AD). To extend these findings, several sphingolipids and sphingolipid hydrolases were analyzed in brain samples from AD patients and age-matched normal individuals. We found a pattern of elevated acid sphingomyelinase (ASM) and acid ceramidase (AC) expression in AD, leading to a reduction in sphingomyelin and elevation of ceramide. More sphingosine also was found in the AD brains, although sphingosine-1-phosphate (S1P) levels were reduced. Notably, significant correlations were observed between the brain ASM and S1P levels and the levels of amyloid beta peptide (Aβ) and phosphorylated tau protein. Based on these findings, neuronal cell cultures were treated with Aβ oligomers, which were found to activate ASM, increase ceramide, and induce apoptosis. Pretreatment of the neurons with purified, recombinant AC prevented the cells from undergoing Aβ-induced apoptosis. We propose that ASM activation is an important pathological event leading to AD, perhaps due to Aβ deposition. The downstream consequences of ASM activation are elevated ceramide, activation of ceramidases, and production of sphingosine. The reduced levels of S1P in the AD brain, together with elevated ceramide, likely contribute to the disease pathogenesis.

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Protective effects of S-nitrosoglutathione against amyloid β-peptide neurotoxicity

Cited by 91 publications

References 47 publications

Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease

Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease

Cellular Stress Response: A Novel Target for Chemoprevention and Nutritional Neuroprotection in Aging, Neurodegenerative Disorders and Longevity

Deregulation of sphingolipid metabolism in Alzheimer's disease

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