Alpha-tocopherol quinone inhibits beta-amyloid aggregation and cytotoxicity, disaggregates preformed fibrils and decreases the production of reactive oxygen species, NO and inflammatory cytokines

Yang, Sherry; Wang, Weiyun; Ling, Tie-Jun; Feng, Ying; Du, Xueting; Zhang, Xi; Sun, Xiaoxia; Zhao, Min; Xue, Ding; Yang, Yang; Liu, Rui‐tian

doi:10.1016/j.neuint.2010.09.011

Cited by 70 publications

(57 citation statements)

References 98 publications

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“…In β-amyloid model, natural quinones such as pyrroloquinoline quinone and α-tocopherol quinone were reported as effective amyloid inhibitors on aggregation3557. Simple quinones in our study, including the first time studied 9,10-phenanthraquinone, may act as functional skeleton entities that contribute to the inhibitory effect of natural quinones.…”

Section: Discussionmentioning

confidence: 67%

Effects of several quinones on insulin aggregation

Gong

Peng

et al. 2014

Sci Rep

127

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Protein misfolding and aggregation are associated with more than twenty diseases, such as neurodegenerative diseases and metabolic diseases. The amyloid oligomers and fibrils may induce cell membrane disruption and lead to cell apoptosis. A great number of studies have focused on discovery of amyloid inhibitors which may prevent or treat amyloidosis diseases. Polyphenols have been extensively studied as a class of amyloid inhibitors, with several polyphenols under clinical trials as anti-neurodegenerative drugs. As oxidative intermediates of natural polyphenols, quinones widely exist in medicinal plants or food. In this study, we used insulin as an amyloid model to test the anti-amyloid effects of four simple quinones and four natural anthraquinone derivatives from rhubarb, a traditional herbal medicine used for treating Alzheimer's disease. Our results demonstrated that all eight quinones show inhibitory effects to different extent on insulin oligomerization, especially for 1,4-benzoquinone and 1,4-naphthoquinone. Significantly attenuated oligomerization, reduced amount of amyloid fibrils and reduced hemolysis levels were found after quinones treatments, indicating quinones may inhibit insulin from forming toxic oligomeric species. The results suggest a potential action of native anthraquinone derivatives in preventing protein misfolding diseases, the quinone skeleton may thus be further explored for designing effective anti-amyloidosis compounds.

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Section: Discussionmentioning

confidence: 67%

Effects of several quinones on insulin aggregation

Gong

Peng

et al. 2014

Sci Rep

127

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“…The RRR-α-tocopherol quinone component inhibited Aβ 42 fibril formation while α-tocopherol failed to do so. [22]. In humans, higher plasma vitamin E was associated with lower AD incidence and combination of vitamin E forms related to neuroprotection [24].…”

Section: Discussionmentioning

confidence: 99%

Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive Function in AβPP/PS1 Mice

Ibrahim

Yanagisawa

Durani

et al. 2016

JAD

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Alzheimer’s disease (AD) is the most common cause of dementia. The cardinal neuropathological characteristic of AD is the accumulation of amyloid-β (Aβ) into extracellular plaques that ultimately disrupt neuronal function and lead to neurodegeneration. One possible therapeutic strategy therefore is to prevent Aβ aggregation. Previous studies have suggested that vitamin E analogs slow AD progression in humans. In the present study, we investigated the effects of the tocotrienol-rich fraction (TRF), a mixture of vitamin E analogs from palm oil, on amyloid pathology in vitro and in vivo. TRF treatment dose-dependently inhibited the formation of Aβ fibrils and Aβ oligomers in vitro. Moreover, daily TRF supplementation to AβPPswe/PS1dE9 double transgenic mice for 10 months attenuated Aβ immunoreactive depositions and thioflavin-S-positive fibrillar type plaques in the brain, and eventually improved cognitive function in the novel object recognition test compared with control AβPPswe/PS1dE9 mice. The present result indicates that TRF reduced amyloid pathology and improved cognitive functions, and suggests that TRF is a potential therapeutic agent for AD.

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“…Therefore, antioxidants taken as supplements, such as vitamin E, vitamin C, coenzyme Q10, and "-carotene, have been tested to prevent and treat AD. However, the supplements have been found to be ineffective at reducing AD symptoms (Yang et al 2010). Some studies have shown that A" peptides can induce the formation of free radicals while others have shown that A" peptides may serve as antioxidants and compensate for the increased oxidative stress in cells.…”

Section: Anti-oxidative Therapymentioning

confidence: 99%

Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

Thapa

2015

Advances in Experimental Medicine and Biology

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Flavonoids are naturally occurring phytochemicals found in a variety of fruits and vegetables and offer color, flavor, aroma, nutritional and health benefits. Flavonoids have been found to play a neuroprotective role by inhibiting and/or modifying the self-assembly of the amyloid-β (Aβ) peptide into oligomers and fibrils, which are linked to the pathogenesis of Alzheimer's disease. The neuroprotective efficacy of flavonoids has been found to strongly depend on their structure and functional groups. Flavonoids may exist in monomeric, as well as di-, tri-, tetra- or polymeric form through C-C or C-O-C linkages. It has been shown that flavonoids containing two or more units, e.g., biflavonoids, exert greater biological activity than their respective monoflavonoids. For instance, biflavonoids have the ability to distinctly alter Aβ aggregation and more effectively reduce the toxicity of Aβ oligomers compared to the monoflavonoid moieties. Although the molecular mechanisms remain to be elucidated, flavonoids have been shown to alter the Aβ aggregation pathway to yield non-toxic, unstructured Aβ aggregates, as well as directly exerting a neuroprotective effect to cells. In this chapter, we review biflavonoid-mediated Aβ aggregation and toxicity, and highlight the beneficial roles biflavonoids can potentially play in the prevention and treatment of Alzheimer's disease.

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Alpha-tocopherol quinone inhibits beta-amyloid aggregation and cytotoxicity, disaggregates preformed fibrils and decreases the production of reactive oxygen species, NO and inflammatory cytokines

Cited by 70 publications

References 98 publications

Effects of several quinones on insulin aggregation

Effects of several quinones on insulin aggregation

Tocotrienol-Rich Fraction Modulates Amyloid Pathology and Improves Cognitive Function in AβPP/PS1 Mice

Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

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