Eicosapentaenoic acid and docosahexaenoic acid increase the degradation of amyloid-β by affecting insulin-degrading enzyme

2016 ◽  
Vol 94 (6) ◽  
pp. 534-542 ◽  
Author(s):  
Marcus O.W. Grimm ◽  
Janine Mett ◽  
Christoph P. Stahlmann ◽  
Viola J. Haupenthal ◽  
Tamara Blümel ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Proteolytic Processing ◽  
Omega 3 ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Aβ Degradation

Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to be highly beneficial in Alzheimer’s disease (AD). AD pathology is closely linked to an overproduction and accumulation of amyloid-β (Aβ) peptides as extracellular senile plaques in the brain. Total Aβ levels are not only dependent on its production by proteolytic processing of the amyloid precursor protein (APP), but also on Aβ-clearance mechanisms, including Aβ-degrading enzymes. Here we show that the omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) increase Aβ-degradation by affecting insulin-degrading enzyme (IDE), the major Aβ-degrading enzyme secreted into the extracellular space of neuronal and microglial cells. The identification of the molecular mechanisms revealed that EPA directly increases IDE enzyme activity and elevates gene expression of IDE. DHA also directly stimulates IDE enzyme activity and affects IDE sorting by increasing exosome release of IDE, resulting in enhanced Aβ-degradation in the extracellular milieu. Apart from the known positive effect of DHA in reducing Aβ production, EPA and DHA might ameliorate AD pathology by increasing Aβ turnover.

scholarly journals Degradation of Alzheimer’s Amyloid-β by a Catalytically Inactive Insulin Degrading Enzyme

2020 ◽  
Author(s):  
Bikash R. Sahoo ◽  
Wenguang Liang ◽  
Wei-Jen Tang ◽  
Ayyalusamy Ramamoorthy
Keyword(s):  
High Speed ◽  
Amyloid Β ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Diffusion Nmr ◽  
Zinc Removal ◽  
Aβ Aggregation ◽  
Aβ Degradation

AbstractInsulin-degrading-enzyme (IDE) is a key target to treat type-2 diabetes, and also known to clear Alzheimer’s amyloid-β (Aβ). However, the development of catalytically inactive IDE mutant (E111QIDE) could risk Aβ clearance. Here, we demonstrate Aβ degradation by E111QIDE and the removal of zinc from the toxic Aβ-Zn complex enabling proteolysis by IDE. Fluorescence and NMR results show delays in Aβ aggregation by both wild-type and E111QIDE in their zinc-bound and unbound states. Diffusion NMR and LC-MS revealed the delayed kinetics is due to Aβ degradation. Remarkably, IDEs exhibited no proteolysis against zinc bound Aβ species as evidenced from high-speed AFM, electron microscopy, chromatography and NMR. On the other hand, zinc removal from the Zn-Aβ complex enabled the proteolysis by IDEs. These findings highlight the role of zinc in switching on/off the proteolysis of Aβ and urge the development potent zinc chelators as a strategic alternative therapeutic for AD.Graphical abstract

Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis

2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Huifeng Zhang ◽  
Dan Liu ◽  
Huanhuan Huang ◽  
Yujia Zhao ◽  
Hui Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Enzyme Activity ◽  
Protein Level ◽  
Senile Plaque ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Significant Difference

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.

scholarly journals Resveratrol Sustains Insulin-Degrading Enzyme Activity toward Aβ42

ACS Omega ◽  
2018 ◽  
Vol 3 (10) ◽  
pp. 13275-13282 ◽  
Author(s):  
Claire A. Krasinski ◽  
Valerie A. Ivancic ◽  
Qiuchen Zheng ◽  
Donald E. Spratt ◽  
Noel D. Lazo
Keyword(s):  
Enzyme Activity ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Insulin Degrading Enzyme Activity

Recent progress on immobilization technology in enzymatic conversion of marine by-products to concentrated omega-3 fatty acids

2021 ◽  
Author(s):  
Yi Liu ◽  
Deepika Dave
Keyword(s):  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
Recent Progress ◽  
Enzymatic Conversion ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Immobilization Technology ◽  
By Products

Marine by-products (heads, frames, trimmings, viscera, skin and scales) have been extensively investigated as sources of marine omega-3 fatty acids (mainly eicosapentaenoic acid and docosahexaenoic acid). Traditionally, extraction of fish...

scholarly journals A Higher Proportion of Eicosapentaenoic Acid (EPA) When Combined with Docosahexaenoic Acid (DHA) in Omega-3 Dietary Supplements Provides Higher Antioxidant Effects in Human Retinal Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 828 ◽  
Author(s):  
Manuel Saenz de Viteri ◽  
María Hernandez ◽  
Valentina Bilbao-Malavé ◽  
Patricia Fernandez-Robredo ◽  
Jorge González-Zamora ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
Cell Viability ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Ethyl Esters ◽  
Omega 3 ◽  
Rpe Cells ◽  
Antioxidant Effects

Retinal pigment epithelium (RPE) is a key regulator of retinal function and is directly related to the transport, delivery, and metabolism of long-chain n-3 polyunsaturated fatty acids (n3-PUFA), in the retina. Due to their functions and location, RPE cells are constantly exposed to oxidative stress. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown to have antioxidant effects by different mechanisms. For this reason, we designed an in vitro study to compare 10 formulations of DHA and EPA supplements from different origins and combined in different proportions, evaluating their effect on cell viability, cell proliferation, reactive oxygen species production, and cell migration using ARPE-19 cells. Furthermore, we assessed their ability to rescue RPE cells from the oxidative conditions seen in diabetic retinopathy. Our results showed that the different formulations of n3-PUFAs have a beneficial effect on cell viability and proliferation and are able to restore oxidative induced RPE damage. We observed that the n3-PUFA provided different results alone or combined in the same supplement. When combined, the best results were obtained in formulations that included a higher proportion of EPA than DHA. Moreover, n3-PUFA in the form of ethyl-esters had a worse performance when compared with triglycerides or phospholipid based formulations.

scholarly journals Supplementation with high-dose docosahexaenoic acid increases the Omega-3 Index more than high-dose eicosapentaenoic acid

2017 ◽  
Vol 120 ◽  
pp. 8-14 ◽  
Author(s):  
Janie Allaire ◽  
William S. Harris ◽  
Cécile Vors ◽  
Amélie Charest ◽  
Johanne Marin ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
High Dose ◽  
Omega 3
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