Effects of docosahexaenoic acid on in vitro amyloid beta peptide 25–35 fibrillation

Hashimoto, Michio; Hossain, Shahdat; Katakura, Masanori; Tanabe, Yoko; Gamoh, Shuji; Miwa, Koichi; Shimada, Toshio; Shido, Osamu

doi:10.1016/j.bbalip.2009.01.012

Cited by 33 publications

(36 citation statements)

References 47 publications

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“…Formation of fibers is thus central to AD pathogenesis, and a great deal of work using various techniques, including transmission electron microscopy [5], atomic force microscopy [6][7][8], circular dichcoism [9], polyacrylamide gel electrophoresis (PAGE) [10][11][12], size-exclusion chromatography [13,14], and quantitative fluorimetry [5,15], has been performed to delineate the mechanism. Consistent with the findings of other studies [16][17][18][19], we have previously reported that Aβ fibrillation involves conformational changes from α helix to β sheet and passes through various phases of fibrillation, including the formation of dimers, trimers, tetramers, oligomers, and finally matured fibrils, using thioflavin T fluorospectroscopy, PAGE, western blot, fluorescence microscopy, and transmission electron microscopy [20][21][22][23]. The natural plant compounds includeing curcumin, epigallocatechin-3-gallate and/or Ginkgo biloba extract and also fish oil components such as docosahexaenoic acid (DHA) were reported to inhibit amyloid formation [24][25][26].…”

Section: Introductionsupporting

confidence: 76%

“…Among these compounds, DHA is the most abundant n-3 polyunsaturated fatty acid (PUFA) in the mammalian brain [27][28][29], and deficiency of DHA is associated with memory impairment in AD model rats [30] and AD patients [31]. Oral administration of DHA decreases the amyloid burden in the brains of AD model rats [30] and mice [32], with a concomitant in vitro inhibition of the amyloid fibril formation, by acting at various stages of polymerization [20][21][22][23]. As one of the mechanism(s) of DHA action, we have previously shown that DHA inhibits in vitro Aβ 1-42 fibrillation at the trimer/tetramer level, and thereby inhibits further progression of lateral stacking of these intermediates and finally prevents mature amyloid fibril formation [20,21].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the inhibitory effect of docosahexaenoic acid and arachidonic acid on the initial stage of amyloid β1-42 polymerization by fluorescence correlation spectroscopy

Miwa¹,

Hashimoto²,

Hossain³

et al. 2013

AAD

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Amyloid β (Aβ) 1-42 fibrillation is a crucial step in the development of pathological hallmarks, such as neuritic plaques and neurofibrillary tangles, of Alzheimer's disease (AD). In this study, we evaluated the effects of free docosahexaenoic acid (DHA), an essential brain polyunsaturated fatty acid (PUFA), on the inhibition of Aβ 1-42 fibrillation by fluorescence correlation spectroscopy (FCS), a technique capable of detecting molecular movements and interactions in solution. We also examined whether free arachidonic acid (AA), eicosapentaenoic acid (EPA), and metabolites of DHA, including neuroprotectin D1 (NPD1, 10S, 17S-dihydroxy-DHA), resolvin D1 (RvD1, 7S, 8R, 17S-trihydroxy-DHA), and didocosahexaenoyl glycerol (diDHA), affect Aβ 1-42 polymerization. The results of the FCS study reveal that DHA and AA significantly reduced the diffusion time of TAMRA (5-carboxytetramethylrhodamine)-Aβ 1-42 by 28% and 31%, respectively, while EPA, NPD1, RvD1, and diDHA had no effects on diffusion time. These results indicate that DHA and AA inhibited Aβ 1-42 polymerization and that their inhibitory effects occurred at the initial stage of Aβ 1-42 polymerization. This study will advance the research on PUFAs in preventing AD progression.

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Section: Introductionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Evaluation of the inhibitory effect of docosahexaenoic acid and arachidonic acid on the initial stage of amyloid β1-42 polymerization by fluorescence correlation spectroscopy

Miwa¹,

Hashimoto²,

Hossain³

et al. 2013

AAD

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“…DHA (5.0-20 lM) significantly inhibited the in vitro fibrillation of Ab 1-42 , Ab , and Ab [25][26][27][28][29][30][31][32][33][34][35] , as determined by ThT-fluorescence fluorospectrometry, laser-confocal microfluorescence and transmission electron microscopy (TEM) (Figure 11) [127][128][129]. By Western blotting, it was found that DHA inhibits the Ab 1-40/42 at the di-to-tetramer species [127,129], while Ab [25][26][27][28][29][30][31][32][33][34][35] was inhibited at the decamer level during their route to matured fibers [128]. Recent findings suggest that soluble Ab oligomers, rather than matured-fibrils, correlate intensely with neuronal dysfunction, damage and AD symptoms [130].…”

Section: Amyloid Fibrillation In Vitro and The Effects Of Dhamentioning

confidence: 99%

Docosahexaenoic acid: one molecule diverse functions

Hashimoto

Hossain

Mamun

et al. 2016

Critical Reviews in Biotechnology

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Docosahexaenoic acid (DHA, C22:6, x-3) is a highly polyunsaturated omega-3 fatty acid. It is concentrated in neuronal brain membranes, for which reason it is also referred to as a ''brain food''. DHA is essential for brain development and function. It plays an important role in improving antioxidant and cognitive activities of the brain. DHA deficiency occurs during aging and dementia, impairs memory and learning, and promotes age-related neurodegenerative diseases, including Alzheimer's disease (AD). For about two decades, we have reported that oral administration of DHA increases spatial memory acquisition, stimulates neurogenesis, and protects against and reverses memory impairment in amyloid b peptide-infused AD rat models by decreasing amyloidogenesis and protects against age-related cognitive decline in the elderly. These results demonstrate a robust link between DHA and cognitive health. Rodents that were fed a diet low in x-3 polyunsaturated fatty acids, particularly those that were DHA-deficient, frequently suffered from anxiety, depression and memory impairment. Although the exact mechanisms of action of DHA in brain functions are still elusive, a host of mechanisms have been proposed. For example, DHA, which inherently has a characteristic three-dimensional structure, increases membrane fluidity, strengthens antioxidant activity and enhances the expression of several proteins that act as substrates for improving memory functions. It reduces the brain amyloid burden and inhibits in vitro fibrillation and amyloid-induced neurotoxicity in cell-culture model. In this review, we discuss how DHA acts as a molecule with diverse functions. ARTICLE HISTORY

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“…Because AD has been shown to be associated with decreased Docosahexaenoic Acid (DHA) levels [19] [20], numerous human trials are currently ongoing to determine whether DHA is effective in the treatment and/or delaying the symptoms of AD [21] [22]. We also reported that DHA decreases amyloid burden in the brains of Aβ-infused model rats [14] [15] and inhibits in vitro amyloid fibrillation [16] [18]. These investigations highlight the potential for DHA as an excellent therapeutic agent against Aβ-induced neurodegenerative diseases, including AD.…”

Section: Introductionmentioning

confidence: 82%

“…Indeed, AD animal models can be produced by brain ventricular infusion of Aβ [12] [13]. Moreover, other fragments of Aβs, such as Aβ [14]- [16] and Aβ [25][26][27][28][29][30][31][32][33][34][35] [17], have also been shown to assemble into amyloid fibers in vitro [16] [18] and have been infused into rat brain ventricles to create AD animal models. Because AD has been shown to be associated with decreased Docosahexaenoic Acid (DHA) levels [19] [20], numerous human trials are currently ongoing to determine whether DHA is effective in the treatment and/or delaying the symptoms of AD [21] [22].…”

Section: Introductionmentioning

confidence: 99%

Computational Analyses of Docosahexaenoic Acid (DHA, C22:6, n-3) with Alzheimer’s Disease-Causing Amyloid Peptide A<i>β</i><sub>1-42</sub> Reassures Its Therapeutic Utility

Hashimoto¹,

Hossain²,

Matsuzaki³

et al. 2016

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The accumulation of amyloid β peptide1-42 (Aβ1-42) masses in the brains of Alzheimer's Disease (AD) patients is associated with neuronal loss and memory deficits. We have previously reported that oral administration of docosahexaenoic acid (DHA, C22:6, n-3) significantly decreases Aβ burden in the brains of AD model rats and that direct in vitro incubation of DHA with Aβ1-42 curbs the progression of amyloid fibrillation. In the present in silico study, we investigated whether DHA computationally binds with amyloid peptides. The NMR solution structures of Aβ1-42 were downloaded from the Protein Data Bank (PDB IDs: 1Z0Q and 2BEG). The binding of DHA to Aβ peptides was assessed by molecular docking using both a flexible and rigid docking system. Thioflavin T (ThT) was used as positive control. The chemical structures of ThT and DHA were modeled and converted to the PDB format using PRODRUG. Drug-like properties of DHA were evaluated by ADME (Absorption, Distribution, Metabolism, and Excretion). DHA was found to successfully dock with Aβ1-42. Computational analyses of the binding of DHA to Aβ1-42, as evaluated by docking studies, further corroborated the inhibitory effect of DHA on in vitro Aβ1-42 fibrillogenesis and might explain the in vivo reduction of amyloid burden observed in the brains of DHA-administered AD model rats demonstrated in our previous study. These computational data suggest the potential utility of DHA as a preventive medication in Aβ-induced neurodegenerative diseases, including AD.

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Effects of docosahexaenoic acid on in vitro amyloid beta peptide 25–35 fibrillation

Cited by 33 publications

References 47 publications

Evaluation of the inhibitory effect of docosahexaenoic acid and arachidonic acid on the initial stage of amyloid β1-42 polymerization by fluorescence correlation spectroscopy

Evaluation of the inhibitory effect of docosahexaenoic acid and arachidonic acid on the initial stage of amyloid β1-42 polymerization by fluorescence correlation spectroscopy

Docosahexaenoic acid: one molecule diverse functions

Computational Analyses of Docosahexaenoic Acid (DHA, C22:6, n-3) with Alzheimer’s Disease-Causing Amyloid Peptide A<i>β</i><sub>1-42</sub> Reassures Its Therapeutic Utility

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Effects of docosahexaenoic acid on in vitro amyloid beta peptide 25–35 fibrillation

Cited by 33 publications

References 47 publications

Evaluation of the inhibitory effect of docosahexaenoic acid and arachidonic acid on the initial stage of amyloid β1-42 polymerization by fluorescence correlation spectroscopy

Evaluation of the inhibitory effect of docosahexaenoic acid and arachidonic acid on the initial stage of amyloid β1-42 polymerization by fluorescence correlation spectroscopy

Docosahexaenoic acid: one molecule diverse functions

Computational Analyses of Docosahexaenoic Acid (DHA, C22:6, n-3) with Alzheimer’s Disease-Causing Amyloid Peptide A&lt;i&gt;β&lt;/i&gt;&lt;sub&gt;1-42&lt;/sub&gt; Reassures Its Therapeutic Utility

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Computational Analyses of Docosahexaenoic Acid (DHA, C22:6, n-3) with Alzheimer’s Disease-Causing Amyloid Peptide A<i>β</i><sub>1-42</sub> Reassures Its Therapeutic Utility