Curcumin derivative with the substitution at C-4 position, but not curcumin, is effective against amyloid pathology in APP/PS1 mice

Yanagisawa, Daijiro; Ibrahim, Nor Faeizah; Taguchi, Hiroyasu; Morikawa, Shigehiro; Hirao, Koichi; Shirai, Nobuyuki; Sogabe, Takayuki; Tooyama, Ikuo

doi:10.1016/j.neurobiolaging.2014.07.041

Cited by 65 publications

(63 citation statements)

References 38 publications

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“…Natural products like curcumin (10) (IC 50 B 13.3 mM), resveratrol (11) (IC 50 B 15.1 mM), and epigallocatechin-3-gallate (12) (EGCG) (IC 50 B 2.4 AE 0.4 mM) have been shown to be effective in decreasing the load of Ab plaques in the brain through their antioxidant and aggregation inhibition properties. 102 APPswe/PS1dE9 double transgenic mice fed with 13a for 6 months showed reduction in the insoluble Ab deposits and reduced cognitive deficits as compared to the animals receiving curcumin or 13b in their diet. Recently, Tooyama et al performed structural modification in curcumin by introducing alkyl (propyl) ester and its corresponding acid at the C 4 -position to obtain FMeC1 (13a) and FMeC2 (13b), respectively (Fig.…”

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confidence: 92%

Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer's disease

2015

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Amyloidogenesis has been implicated in a broad spectrum of diseases in which amyloid protein is invariably misfolded and deposited in cells and organs. Alzheimer's disease is one of the most devastating ailments among amyloidogenesis induced dementia. The amyloid beta (Aβ) peptide derived from amyloid precursor protein (APP) is misfolded and deposited as plaques in the brain, which are said to be the hallmark of Alzheimer's disease. In normal brains physiological concentration of the Aβ peptide has been indicated to be involved in modulating neurogenesis and synaptic plasticity. However, excess Aβ production, its aggregation and deposition deleteriously affect a large number of biologically important pathways leading to neuronal cell death. Targeting Aβ production, Aβ aggregation or its clearance from the brain has been an active area of research for preventing or curing AD. Our Feature Article intends to detail the aggregation mechanism, the physiological role of the Aβ peptide, elaborate its toxic effects, and outline the different classes of molecules designed in the last two years to inhibit amyloidogenic APP processing, Aβ oligomerization or fibrillogenesis and to modulate different pathways for active clearance of Aβ from the brain.

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Section: View Article Onlinementioning

confidence: 92%

Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer's disease

2015

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“…Human Aβ 1-42 peptide (Aβ 42 , Peptide Institute, Osaka, Japan) was dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) at 1 mM [31]. The mixture was then incubated at 37°C for 1 h, aliquoted into microcentrifuge tubes and evaporated for 30 min in an evaporation chamber.…”

Section: Methodsmentioning

confidence: 99%

“…The rest of the mice were employed for other experiments. Mice were sacrificed at 15 months of age by cervical dislocation and brain tissue prepared as described previously [31]. In brief, the brain was removed and divided into two hemispheres.…”

Section: Methodsmentioning

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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“…Among these, APP/PS1 double transgenic mice are an extensively used model, showing progressive age-related development of Aβ accumulation and cognitive deficits (Jankowsky et al 2001;Trinchese et al 2004;van Groen et al 2006;Meyer-Luehmann et al 2009;Filali et al 2011;Janus et al 2015). Furthermore, previous studies have revealed positive results, such as demonstrating various antioxidants (Garcia-Alloza et al 2010;Varamini et al 2014;Yanagisawa et al 2015), neuroprotective agents (Kilgore et al 2010;Peng et al 2012;Li et al 2014), anti-neuroinflammation (Cherry et al 2015;Guo et al 2015), immune therapy (Sudduth et al 2013;Carrera et al 2013;Zhang et al 2015), and nonpharmacological interventions (Liu et al 2011;Jankowsky et al 2005), which can attenuate or even reserve AD-like pathology in APP/PS1 mice. Unfortunately, none of these potentially useful results have been able to be reproduced in clinical therapies for AD patients.…”

Section: Introductionmentioning

confidence: 99%

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

Huang

Nie

Cao

et al. 2016

AGE

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Transgenic APPSwe/PS1dE9 (APP/PS1) mice that overproduce amyloid beta (Aβ) are extensively used in the studies of pathogenesis and experimental therapeutics and new drug screening for Alzheimer's disease (AD). However, most of the current literature uses young or adult APP/PS1 mice. In order to provide a broader view of AD-like phenotype of this animal model, in this study, we systematically analyzed behavioral and pathological profiles of 24-month-old male APP/ PS1 mice. Aged APP/PS1 mice had reference memory deficits as well as anxiety, hyperactivity, and social interaction impairment. Consistently, there was obvious deposition of amyloid plaques in the dorsal hippocampus with decreased expression of insulin-degrading enzyme, a proteolytic enzyme responsible for degradation of intracellular Aβ. Furthermore, decreases in hippocampal volume, neuronal number and synaptophysin expression, and astrocyte atrophy were also observed in aged APP/PS1 mice. This finding suggests that aged APP/PS1 mice can well replicate cognitive and noncognitive behavioral abnormalities, hippocampal atrophy, and neuronal and astrocyte degeneration in AD patients, to enable more objective and refined preclinical evaluation of therapeutic drugs and strategies for AD treatment.

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Curcumin derivative with the substitution at C-4 position, but not curcumin, is effective against amyloid pathology in APP/PS1 mice

Cited by 65 publications

References 38 publications

Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer's disease

Function and toxicity of amyloid beta and recent therapeutic interventions targeting amyloid beta in Alzheimer's disease

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

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

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