Amyloid β-peptide and amyloid pathology are central to the oxidative stress and inflammatory cascades under which Alzheimer's disease brain exists

Butterfield, D. Allan; Griffin, Sue T.; Münch, Gerald; Pasinetti, Giulio Maria

doi:10.3233/jad-2002-4309

Cited by 155 publications

(106 citation statements)

References 96 publications

(101 reference statements)

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“…Most believe that Aβ toxicity is linked to the formation of aggregated species, with the most toxic species being an intermediate between monomer and fibrils [11][12][13][14]. Some believe that Aβ acts via association with the cell membrane [15], to cause membrane depolarization, changes in membrane capacitance [16], membrane destabilization [17], pore formation [18,19] or free radical generation [20,21]. Consistent with these observations is that the first step in Aβ toxicity is Aβ binding to a membrane component.…”

Section: Introductionsupporting

confidence: 56%

Development of photocrosslinked sialic acid containing polymers for use in Aβ toxicity attenuation

2008

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Abstractβ-Amyloid peptide (Aβ), the primary protein component in senile plaques associated with Alzheimer's disease (AD), has been implicated in neurotoxicity associated with AD. Previous studies have shown that the Aβ-neuronal membrane interaction plays a crucial role in Aβ toxicity. More specifically, it is thought that Aβ interacts with ganglioside rich and sialic acid rich regions of cell surfaces. In light of such evidence, we have hypothesized that the Aβ-membrane sialic acid interaction could be inhibited through use of a biomimic multivalent sialic acid compound that would compete with the cell surface for Aβ binding. To explore this hypothesis, we synthesized a series of photocrosslinked sialic acid containing oligosaccharides and tested their ability to bind Aβ and attenuate Aβ toxicity in cell culture assays. We show that a polymer prepared via the photocrosslinking of disialyllacto-N-tetraose (DSLNT) was able to attenuate Aβ toxicity at low micromolar concentrations without adversely affecting the cell viability. Polymers prepared from mono-sialyl-oligosaccharides were less effective at Aβ toxicity attenuation. These results demonstrate the feasibility of using photocrosslinked sialyl-oligosaccharides for prevention of Aβ toxicity in vitro and may provide insight into the design of new materials for use in attenuation of Aβ toxicity associated with AD.

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Section: Introductionsupporting

confidence: 56%

Development of photocrosslinked sialic acid containing polymers for use in Aβ toxicity attenuation

2008

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“…In the aging canine, no significant correlation between the levels of Aβ deposition in brain and oxidative damage is observed [54], however, since the aging canine deposits the more toxic form of Aβ 1-42 as that seen in human aging [19,74] and since Aβ load and decline in cognitive function events develop in parallel, Aβ could still play a significant role in the mechanism of oxidative stress observed in the aging canine [42,43,52]. In the peptide sequence of Aβ (1-42), there is a methionine-35 residue that our laboratory has shown to play a critical role in Aβ induced oxidative stress and neurotoxicity observed in AD [24].…”

Section: Discussionmentioning

confidence: 99%

Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's disease

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Joshi

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et al. 2008

Neurobiology of Aging

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Aging and age-related disorders such as Alzheimer's disease (AD) are usually accompanied by oxidative stress as one of the main mechanisms contributing to neurodegeneration and cognitive decline. Aging canines develop cognitive dysfunction and neuropathology similar to those seen in humans, and the use of antioxidants results in reductions in oxidative damage and in improvement in cognitive function in this canine model of human aging. In the present study, the effect of a longterm treatment with an antioxidant fortified diet and a program of behavioral enrichment on oxidative damage was studied in aged canines. To identify the neurobiological mechanisms underlying these treatment effects, the parietal cortex from 23 beagle dogs (8.1-12.4 years) were treated for 2.8 years in one of four treatment groups: i.e., control food-control behavioral enrichment (CC); control food -behavioral enrichment (CE); antioxidant food-control behavioral enrichment (CA); and enriched environment -antioxidant fortified food (EA). We analyzed the levels of the oxidative stress biomarkers, i.e., protein carbonyls, 3-nitrotyroine (3NT), and the lipid peroxidation product, 4- Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeurobiol Aging. Author manuscript; available in PMC 2009 January 1. Published in final edited form as:Neurobiol Aging. 2008 January ; 29(1): 51-70. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript hydroxynonenal (HNE), and observed a decrease in their levels on all treatments when compared to control, with the most significant effects found in the combined treatment, EA. Since EA treatment was most effective, we also carried out a comparative proteomics study to identify specific brain proteins that were differentially expressed and used a parallel redox proteomics approach to identify specific brain proteins that were less oxidized following EA. The specific protein carbonyl levels of glutamate dehydrogenase [NAD (P)], glyceraldehyde-3-phosphate dehydrogenase (GAPDH), α-enolase, neurofilament triplet L protein, glutathione S-transferase (GST) and fascin actin bundling protein were significantly reduced in brain of EA-treated dogs compared to control. We also observed significant increases in expression of Cu/Zn superoxide dismutase, fructose-bisphosphate aldolase C, creatine kinase, glutamate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase. The increased expression of these proteins and in particular Cu/Zn SOD correlated with improved cognitive function. In addition, there was a significant increas...

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“…The view that Aβ plays a central role in AD pathogenesis has developed from observations that patients with mutations in the APP and presenilin (PSEN) genes show both accelerated plaque deposition and the onset of dementia at an early age, and that all these patients demonstrate an increase in the production of Aβ, particularly the longer and more aggregation prone Aβ 1-42 (Butterfield et al 2002). by the immune system Robinson et al 2004;Dasilva et al 2006;Panza et al 2010).…”

Section: Anti-amyloid Drugsmentioning

confidence: 99%

Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

et al. 2012

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The use of induced pluripotent stem cells (iPSCs), whereby a patient's somatic cells can be reprogrammed to a pluripotent state by the forced expression of a defined set of transcription factors, has the potential to enable in vitro disease modelling and be used for drug discovery programs. Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that leads to a decline in memory and cognition. Fibroblasts were taken from AD patients (or non‐AD controls) and cultured under specific conditions to generate iPSCs which were then provided with growth factors to allow differentiation into neurons. While AD‐iPSCs were morphologically indistinguishable from control‐iPSCs, differentiated cells showed differing responses to both cellular stresses and neuroprotective drugs. Since these cells are derived from individual patients, the use of iPSCs has provided novel insights into disease pathogenesis, providing information on an individual's variations in the disease process and their cellular response to drugs.

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Amyloid β-peptide and amyloid pathology are central to the oxidative stress and inflammatory cascades under which Alzheimer's disease brain exists

Cited by 155 publications

References 96 publications

Development of photocrosslinked sialic acid containing polymers for use in Aβ toxicity attenuation

Development of photocrosslinked sialic acid containing polymers for use in Aβ toxicity attenuation

Proteomic identification of brain proteins in the canine model of human aging following a long-term treatment with antioxidants and a program of behavioral enrichment: Relevance to Alzheimer's disease

Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer’s disease

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