The binding of resveratrol to monomer and fibril amyloid beta

Ge, Jin‐Fang; Qiao, Jie; Qi, Cong-Cong; Wang, Chen-Wei; Zhou, Jiang‐Ning

doi:10.1016/j.neuint.2012.08.012

Cited by 95 publications

(59 citation statements)

References 48 publications

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“…In addition, this observation suggested an effect of the reduced amount of Aβ 40 fibrils in solution that could have acted as seeds to catalyze the Aβ 40 aggregation. As the results from this study were in agreement with previous investigations of resveratrol as Aβ -targeting agents for Alzheimer's disease, [57][58][59] EIS proved to be a useful tool to assist in the elucidation of Aβ aggregation in the presence of small molecule modulators. 40 aggregation with Resveratrol.-Aβ 40 aggregation in the presence and absence of resveratrol was also observed using Thioflavin T (ThT) fluorescence ( Figure 4B).…”

Section: Resultssupporting

confidence: 89%

“…Rather, large, amorphous and seemingly porous structures were found ( Figure 5B). These globular species obtained from our experimental conditions were similar to those observed by other groups [59][60][61][62] and were reported to be nontoxic to PC12 neuronal cells. 63,64 TEM results were in agreement with the collected EIS and fluorescence data.…”

Section: Thioflavin T Assay Of Aβsupporting

confidence: 90%

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Electrochemical Detection of Amyloid-Beta Aggregation in the Presence of Resveratrol

Hung

Cheng

et al. 2013

J. Electrochem. Soc.

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The aggregation of amyloid-β (Aβ) is an important pathologic feature of Alzheimer's disease (AD) that leads to the formation of neuronal plaques. A rapidly growing number of polyphenols have been intensively investigated for AD treatment. In this report, the interaction of a polyphenolic compound, resveratrol, with Aβ was studied using electrochemical impedance spectroscopy (EIS). The growth of Aβ fibrils was facilitated with the incubation of oligomer-modified electrodes with free Aβ in solution. Resveratrol significantly slowed down the formation of Aβ aggregates, which was monitored by following the changes in the charge transfer resistance (R ct ) values. The moderating effect of resveratrol on Aβ aggregation was also confirmed with Thioflavin T (ThT) fluorescence assay and transmission electron microscopy (TEM) imaging. Results obtained from EIS correlated well with the ThT fluorescence assay and suggested that EIS was a promising method for the analysis of Aβ aggregation in the presence of novel Aβ-targeting compounds toward AD therapy. Various factors contribute to the deterioration of health in the aging population. Of those, dementia is a prominent worldwide issue that is currently under intense investigation in an effort to discover novel therapeutic agents to slow the progression of this disease. Alzheimer's disease (AD) has been found to be the most common cause of dementia, in which a multitude of regulatory pathways are affected. As the disease progresses, physical manifestations include reduced mobility, changes in behavior and a decline in cognitive function.

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Section: Resultssupporting

confidence: 89%

Section: Thioflavin T Assay Of Aβsupporting

confidence: 90%

Electrochemical Detection of Amyloid-Beta Aggregation in the Presence of Resveratrol

Hung

Cheng

et al. 2013

J. Electrochem. Soc.

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“…Such effects have been reported in various phenolic compounds: flavones such as baicalein (Caruana et al 2012), flavonols such as Myr, quercetin, and morin (Ono et al 2003(Ono et al , 2006a(Ono et al , 2012Masuda et al 2006;Chakraborty et al 2011;Caruana et al 2012;Ho et al 2013), isoflavones such as glycitein and genistein , flavanols such as EGCG and theaflavins (Ono et al 2003(Ono et al , 2006aLevites et al 2003;Rezai-Zadeh et al 2005;Obregon et al 2006;Bastianetto et al 2006;Ehrnhoefer et al 2008;Bieschke et al 2010;He et al 2011;Grelle et al 2011;Cheng et al 2013;Sinha et al 2012;Rushworth et al 2013;Palhano et al 2013;Lorenzen et al 2014), stilbenes such as resveratrol, nordihydroguaiaretic acid (NDGA), piceid, and viniferin (Ono et al 2002(Ono et al , 2003(Ono et al , 2006a(Ono et al , 2012Savaskan et al 2003;Marambaud et al 2005;Rivière et al 2007Rivière et al , 2009Gauci et al 2011;Capiralla et al 2012;Ge et al 2012;Feng et al 2013;Vingtdeux et al 2010;Caruana et al 2012;Rushworth et al 2013;Richard et al 2013), phenolic acids such as rosmarinic acid (RA), tannic acids (TA), ferulic acid (FA), ellagic aci...…”

Section: Studies Using In Vitro Models Of Cerebral Amyloidosismentioning

confidence: 99%

Natural Phenolic Compounds as Therapeutic and Preventive Agents for Cerebral Amyloidosis

Yamada

Ono

Hamaguchi

et al. 2015

Advances in Experimental Medicine and Biology

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Epidemiological studies have suggested that diets rich in phenolic compounds may have preventive effects on the development of dementia or Alzheimer's disease (AD). We investigated the effects of natural phenolic compounds, such as myricetin (Myr), rosmarinic acid (RA), ferulic acid (FA), curcumin (Cur) and nordihydroguaiaretic acid (NDGA) on the aggregation of amyloid β-protein (Aβ), using in vitro and in vivo models of cerebral Aβ amyloidosis. The in vitro studies revealed that these phenolic compounds efficiently inhibit oligomerization as well as fibril formation of Aβ through differential binding, whilst reducing Aβ oligomer-induced synaptic and neuronal toxicity. Furthermore, a transgenic mouse model fed orally with such phenolic compounds showed significant reduction of soluble Aβ oligomers as well as of insoluble Aβ deposition in the brain. These data, together with an updated review of the literature, indicate that natural phenolic compounds have anti-amyloidogenic effects on Aβ in addition to well-known anti-oxidative and anti-inflammatory effects, hence suggesting their potential as therapeutic and/or preventive agents for cerebral Aβ amyloidosis, including AD and cerebral amyloid angiopathy (CAA). Well-designed clinical trials or preventive interventions with natural phenolic compounds are necessary to establish their efficacy as disease-modifying agents.

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“…Most notably, resveratrol was able to directly interfere with the Aβ aggregation. Resveratrol was proved to directly interact with Aβ monomers and fibrils, inhibit Aβ fibrillization, and convert toxic oligomers into nontoxic species [77,78]. Resveratrol derivatives were also shown to inhibit Aβ42 aggregation by targeting the C-terminus and inhibiting the formation of β-sheets [79].…”

Section: Resveratrolmentioning

confidence: 99%

Anti-amyloid Aggregation Activity of Natural Compounds: Implications for Alzheimer’s Drug Discovery

Rao

Wang

2015

Mol Neurobiol

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Several plant-derived natural compounds are known to exhibit anti-amyloid aggregation activity which makes them attractive as potential therapies to treat Alzheimer's disease. The mechanisms of their anti-amyloid activity are not well known. In this regard, many natural compounds are known to exhibit direct binding to various amyloid species including oligomers and fibrils, which in turn can lead to conformational change in the beta-sheet assembly to form nontoxic aggregates. This review discusses the mechanism of anti-amyloid activity of 16 natural compounds and gives structural details on their direct binding interactions with amyloid aggregates. Our computational investigations show that the physicochemical properties of natural products do fit Lipinski's criteria and that catechol and catechol-type moieties present in natural compounds act as lysine site-specific inhibitors of amyloid aggregation. Based on these observations, we propose a structural template to design novel small molecules containing site-specific ring scaffolds, planar aromatic and nonaromatic linkers with suitably substituted hydrogen bond acceptors and donors. These studies will have significant implications in the design and development of novel amyloid aggregation inhibitors with superior metabolic stability and blood-brain barrier penetration as potential agents to treat Alzheimer's disease.

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The binding of resveratrol to monomer and fibril amyloid beta

Cited by 95 publications

References 48 publications

Electrochemical Detection of Amyloid-Beta Aggregation in the Presence of Resveratrol

Electrochemical Detection of Amyloid-Beta Aggregation in the Presence of Resveratrol

Natural Phenolic Compounds as Therapeutic and Preventive Agents for Cerebral Amyloidosis

Anti-amyloid Aggregation Activity of Natural Compounds: Implications for Alzheimer’s Drug Discovery

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