Inhibition of Alzheimer’s amyloid toxicity with a tricyclic pyrone molecule <i>in vitro</i> and <i>in vivo</i>

Hong, Hyun Seok; Rana, Sandeep; Barrigan, Lydia M.; Shi, Aibin; Zhang, Yi; Zhou, Feimeng; Jin, Lee‐Way; Hua, Duy H.

doi:10.1111/j.1471-4159.2008.05866.x

Cited by 64 publications

(64 citation statements)

References 58 publications

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“…Epidemiological studies have suggested that curcumin contributes to the reported 4.4-fold reduced (age-adjusted) prevalence of AD in India compared with the United States (16). Both in vitro and in vivo studies have shown that curcumin can bind to amyloid and inhibit A␤ aggregation (14,17), as well as fibril and oligomer formation (14). In vivo studies have shown that dietary curcumin can cross the blood-brain barrier and significantly decrease A␤ deposition and plaque burden in AD transgenic mice (14,15,18,19), markedly inhibit Tau phosphorylation (20), and attenuate inflammation and reduce oxidative damage (14,18), and reduce genomic instability events (21).…”

Section: Alzheimer Disease (Ad)mentioning

confidence: 99%

Curcumin Decreases Amyloid-β Peptide Levels by Attenuating the Maturation of Amyloid-β Precursor Protein

Zhang

Browne

Child

et al. 2010

Journal of Biological Chemistry

176

110

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Alzheimer disease (AD) is a devastating neurodegenerative disease with no cure. The pathogenesis of AD is believed to be driven primarily by amyloid-␤ (A␤), the principal component of senile plaques. A␤ is an ϳ4-kDa peptide generated via cleavage of the amyloid-␤ precursor protein (APP). Curcumin is a compound in the widely used culinary spice, turmeric, which possesses potent and broad biological activities, including anti-inflammatory and antioxidant activities, chemopreventative effects, and effects on protein trafficking. Recent in vivo studies indicate that curcumin is able to reduce A␤-related pathology in transgenic AD mouse models via unknown molecular mechanisms. Here, we investigated the effects of curcumin on A␤ levels and APP processing in various cell lines and mouse primary cortical neurons. We show for the first time that curcumin potently lowers A␤ levels by attenuating the maturation of APP in the secretory pathway. These data provide a mechanism of action for the ability of curcumin to attenuate amyloid-␤ pathology.

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Section: Alzheimer Disease (Ad)mentioning

confidence: 99%

Curcumin Decreases Amyloid-β Peptide Levels by Attenuating the Maturation of Amyloid-β Precursor Protein

Zhang

Browne

Child

et al. 2010

Journal of Biological Chemistry

176

110

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“…Solutions of oligomeric Ab 1-42 were prepared as described previously. 49 To prepare the oligomer solution, monomeric Ab 1-42 peptides were incubated with PBS at 4 1C for 24 h and immediately stored in aliquots at À 80 1C. To examine the effect of DBP on oligomeric Ab 1-42 formation, peptide solutions containing Ab 1-42 monomers (10 mM) with and without DBP (100 mg/ml) were incubated at 4 1C for 24 h. DBPfree samples were treated with the same volume of distilled water.…”

Section: Methodsmentioning

confidence: 99%

Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology

et al. 2012

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The level of vitamin D-binding protein (DBP) is increased in the cerebrospinal fluid of patients with Alzheimer's disease (AD), suggesting a relationship with its pathogenesis. In this study, we investigated whether and how DBP is related to AD using several different approaches. A pull-down assay and a surface plasmon resonance binding assay indicated direct interactions between purified DBP and amyloid beta (Ab), which was confirmed in the brain of AD patients and transgenic AD model mice by immunoprecipitation assay and immunohistochemical double-staining method. Moreover, atomic force microscopic examination revealed that DBP reduced Ab aggregation in vitro. DBP also prevented Ab-mediated death in cultured mouse hippocampal HT22 cell line. Finally, DBP decreased Ab-induced synaptic loss in the hippocampus and rescued memory deficits in mice after injection of Ab into the lateral ventricle. These results provide converging evidence that DBP attenuates the harmful effects of Ab by a direct interaction, and suggest that DBP is a promising therapeutic agent for the treatment of AD.

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“…Curcumin is an active principle of the perennial herb Curcuma longa (commonly known as turmeric) which is used in the Indian traditional diet and as herbal medicine [13]. Recent studies indicate a role for curcumin as a potential anti-amyloid agent in vitro [14][15][16] and in vivo [17,18]. However, curcumin is unstable in aqueous media [19] and presents low bioavailability following delivery through oral or parenteral route [20].…”

Section: Introductionmentioning

confidence: 99%

Functionalization with TAT-Peptide Enhances Blood-Brain Barrier Crossing In vitro of Nanoliposomes Carrying a Curcumin-Derivative to Bind Amyloid-Β Peptide

Sancini

Gregori

Salvati

et al. 2013

J Nanomedic Nanotechnol

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# These authors contributed equally to this work preventing high-molecular weight molecules from passing through [25]. Indeed, the design and engineering of NP with high specificity for brain capillary endothelial cells have been proposed as promising strategy for AD diagnosis and treatment [26][27][28][29].The aim of the present investigation was to design NP able to bind Aβ peptide and to cross the BBB. To reach this goal we developed nanoliposomes (NL) double-functionalized with a curcuminderivative and with a modified HIV Transactivating Transcriptional Activator (TAT) peptide. Preparation of NL covalently decorated with curcumin-derivative was previously carried out, starting from a curcumin alkyne-derivative showing a very high affinity for Aβ peptide [30], suitable for NL decoration by click chemistry and with improved features of stability with respect to curcumin itself [31]. On the other side, TAT-peptide could enhance NP BBB crossing [32,33] based on the evidence that its coupling to NP may facilitate their efficient translocation through the cell membrane, bypassing the endocytic pathway [34][35][36]. TAT-peptide was covalently attached to NL surface via a thiol-maleimide reaction. The ability of NL to bind Aβ after AbstractProduction of abnormally high amounts of amyloid-β peptide in the brain plays a central role in the onset and development of Alzheimer's disease, a neurodegenerative disorder affecting millions of individuals worldwide. Nanoparticles have been proposed as promising tools to treat the disease by delivering drugs and contrast agents to the brain. Here, nanoliposomes decorated with a curcumin-derivative, displaying high affinity for amyloid-β, were functionalized with a modified cell-penetrating TAT-peptide, with the aim of conferring on such nanoliposomes the ability to cross the blood-brain barrier. Functionalization with TAT-peptide did not modify the ability of curcumindecorated nanoliposomes to bind amyloid-β fibrils, as assessed by surface plasmon resonance. Confocal microscopy, mass spectrometry and radioactivity experiments with [3 H]-sphingomyelin showed about 3-fold increase in the uptake of nanoliposomes by human brain capillary endothelial cells (hCMEC/D3) after the functionalization with TATpeptide, with no alterations in cell viability. Moreover, TAT functionalization increased the permeability of curcuminnanoliposomes across a blood-brain barrier model made with the same cells. The similar permeabilities of curcuminderivative and [3 H]-sphingomyelin suggested that nanoliposomes were transported intact. Considering these results, nanoliposomes functionalized with the curcumin-derivative and TAT-peptide represent a promising tool for targeting amyloid-β directly in the brain parenchyma.

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Inhibition of Alzheimer’s amyloid toxicity with a tricyclic pyrone molecule in vitro and in vivo

Cited by 64 publications

References 58 publications

Curcumin Decreases Amyloid-β Peptide Levels by Attenuating the Maturation of Amyloid-β Precursor Protein

Curcumin Decreases Amyloid-β Peptide Levels by Attenuating the Maturation of Amyloid-β Precursor Protein

Vitamin D-binding protein interacts with Aβ and suppresses Aβ-mediated pathology

Functionalization with TAT-Peptide Enhances Blood-Brain Barrier Crossing In vitro of Nanoliposomes Carrying a Curcumin-Derivative to Bind Amyloid-Β Peptide

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