Preferential interaction of the Alzheimer peptide Aβ‐(1–42) with Omega‐3‐containing lipid bilayers: structure and interaction studies

Emendato, Alessandro; Spadaccini, Roberta; Santis, Augusta De; Guerrini, Remo; D’Errico, Gerardino; Picone, Delia

doi:10.1002/1873-3468.12082

Cited by 10 publications

(5 citation statements)

References 54 publications

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“…We first explored by systematically screening the effects of buffer, pH, and ionic strength on the kinetics of glycation and self-assembly to find conditions in which aggregation would be sufficiently slow to follow the glycation process using peptides synthesized in house and previously extensively characterized ( 31 ). Optimal conditions for the reaction were found using 200 m m phosphate buffer at pH 7.4, to have a polar environment in which the Aβ peptides are known to quickly aggregate and adopt a β-conformation ( 32 ). The peptides were always pretreated under strong acidic conditions (TFA) for 1 h and freeze-dried to remove the volatile acid.…”

Section: Resultsmentioning

confidence: 99%

Glycation affects fibril formation of Aβ peptides

Emendato

Milordini

Zacco

et al. 2018

Journal of Biological Chemistry

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Increasing evidence shows that β-amyloid (Aβ) peptides, which are associated with Alzheimer disease (AD), are heavily glycated in patients, suggesting a role of this irreversible nonenzymatic post-translational modification in pathology. Previous reports have shown that glycation increases the toxicity of the Aβ peptides, although little is known about the mechanism. Here, we used the natural metabolic by-product methylglyoxal as a glycating agent and exploited various spectroscopic methods and atomic force microscopy to study how glycation affects the structures of the Aβ40 and Aβ42 peptides, the aggregation pathway, and the morphologies of the resulting aggregates. We found that glycation significantly slows down but does not prevent β-conversion to mature fibers. We propose that the previously reported higher toxicity of the glycated Aβ peptides could be explained by a longer persistence in an oligomeric form, usually believed to be the toxic species.

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Section: Resultsmentioning

confidence: 99%

Glycation affects fibril formation of Aβ peptides

Emendato

Milordini

Zacco

et al. 2018

Journal of Biological Chemistry

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“…[46] DHA has recently been shown to have this effect. [47] Hence higher membrane levels of EPA and/or DHA may favorably affect the metabolism of Aβ peptides and thereby reduce risk for AD/D progression.…”

Section: Discussionmentioning

confidence: 99%

Erythrocyte omega-3 fatty acids are inversely associated with incident dementia: Secondary analyses of longitudinal data from the Women's Health Initiative Memory Study (WHIMS)

Ammann

Pottala

Robinson

et al. 2017

Prostaglandins, Leukotrienes and Essential Fatty Acids

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OBJECTIVE To assess whether red blood cell (RBC) docosahexaenoic acid and eicosapentaenoic acid (DHA+EPA) levels have a protective association with the risk of dementia in older women. METHODS RBC DHA+EPA levels were assessed at baseline, and cognitive status was evaluated annually in a cohort of 6706 women aged ≥65 years who participated in the Women’s Health Initiative Memory Study (WHIMS). Cox regression was used to quantify the association between RBC DHA+EPA and the risk of probable dementia, independent of major dementia risk factors. RESULTS During a median follow-up period of 9.8 years, 587 incident cases of probable dementia were identified. After adjusting for demographic, clinical, and behavioral risk factors, a one standard deviation increase in DHA+EPA levels was associated with a significantly lower risk of dementia (HR = 0.92, 95% CI: 0.84, 1.00; p < 0.05). This effect estimate did not meaningfully change after further adjustment for baseline cognitive function and APOE genotype. For women with high DHA+EPA exposure (1 SD above mean) compared to low exposure (1 SD below mean), the adjusted 15-year absolute risk difference for dementia was 2.1% (95% CI: 0.2%, 4.0%). In secondary analyses, we also observed a protective association with longitudinal change in Modified Mini-Mental State (3MS) Exam scores, but no significant association with incident MCI, PD/MCI, or baseline 3MS scores. DISCUSSION Higher levels of DHA+EPA may help protect against the development of dementia. Results from prospective randomized controlled trials of DHA+EPA supplementation are needed to help clarify whether this association is causal.

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“…Favourably, they also have a high ratio of n3-PUFA/n6-PUFA of 1:3 to 1:4 (Vinson and Cai 2012;Poulose et al 2014). n3-PUFA are known to reduce the production of peptide amyloid-beta (Aβ) (Emendato et al 2016;Thomas et al 2015), commonly associated with AD, and additionally improve health of brain cells (Carey et al 2013). For example, in accordance with Cole et al we reported that DHA improved the fluidity of neuronal membranes (Cole et al 2009;Eckert et al 2011).…”

Section: Introductionmentioning

confidence: 70%

A Walnut Diet in Combination with Enriched Environment Improves Cognitive Function and Affects Lipid Metabolites in Brain and Liver of Aged NMRI Mice

et al. 2020

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This in vivo study aimed to test if a diet enriched with 6% walnuts alone or in combination with physical activity supports healthy ageing by changing the oxylipin profile in brain and liver, improving motor function, cognition, and cerebral mitochondrial function. Female NMRI mice were fed a 6% walnut diet starting at an age of 12 months for 24 weeks. One group was additionally maintained in an enriched environment, one group without intervention served as control. After three months, one additional control group of young mice (3 weeks old) was introduced. Motor and cognitive functions were measured using Open Field, Y-Maze, Rotarod and Passive Avoidance tests. Lipid metabolite profiles were determined using RP-LC-ESI(-)-MS/MS in brain and liver tissues of mice. Cerebral mitochondrial function was characterized by the determination of ATP levels, mitochondrial membrane potential and mitochondrial respiration. Expression of genes involved with mito- and neurogenesis, inflammation, and synaptic plasticity were determined using qRT-PCR. A 6% walnut-enriched diet alone improved spatial memory in a Y-Maze alternation test (p < 0.05) in mice. Additional physical enrichment enhanced the significance, although the overall benefit was virtually identical. Instead, physical enrichment improved motor performance in a Rotarod experiment (p* < 0.05) which was unaffected by walnuts alone. Bioactive oxylipins like hydroxy-polyunsaturated fatty acids (OH-PUFA) derived from linoleic acid (LA) were significantly increased in brain (p** < 0.01) and liver (p*** < 0.0001) compared to control mice, while OH-PUFA of α-linolenic acid (ALA) could only be detected in the brains of mice fed with walnuts. In the brain, walnuts combined with physical activity reduced arachidonic acid (ARA)-based oxylipin levels (p < 0.05). Effects of walnut lipids were not linked to mitochondrial function, as ATP production, mitochondrial membrane potential and mitochondrial respiration were unaffected. Furthermore, common markers for synaptic plasticity and neuronal growth, key genes in the regulation of cytoprotective response to oxidative stress and neuronal growth were unaffected. Taken together, walnuts change the oxylipin profile in liver and brain, which could have beneficial effects for healthy ageing, an effect that can be further enhanced with an active lifestyle. Further studies may focus on specific nutrient lipids that potentially provide preventive effects in the brain.

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Preferential interaction of the Alzheimer peptide Aβ‐(1–42) with Omega‐3‐containing lipid bilayers: structure and interaction studies

Cited by 10 publications

References 54 publications

Glycation affects fibril formation of Aβ peptides

Glycation affects fibril formation of Aβ peptides

Erythrocyte omega-3 fatty acids are inversely associated with incident dementia: Secondary analyses of longitudinal data from the Women's Health Initiative Memory Study (WHIMS)

A Walnut Diet in Combination with Enriched Environment Improves Cognitive Function and Affects Lipid Metabolites in Brain and Liver of Aged NMRI Mice

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