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A bifunctional curcumin analogue for two-photon imaging and inhibiting crosslinking of amyloid beta in Alzheimer's disease.

ABSTRACT: In this report, we designed a highly bright bifunctional curcumin analogue CRANAD-28. In vivo two-photon imaging suggested that CRANAD-28 could penetrate the blood brain barrier (BBB) and label plaques and cerebral amyloid angiopathies (CAAs). We also demonstrated that this imaging probe could inhibit the crosslinking of amyloid beta induced either by copper or by natural conditions.

SUBMITTER: Zhang X

PROVIDER: S-EPMC4617557 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other

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A bifunctional curcumin analogue for two-photon imaging and inhibiting crosslinking of amyloid beta in Alzheimer's disease.

Zhang Xueli X Tian Yanli Y Yuan Peng P Li Yuyan Y Yaseen Mohammad A MA Grutzendler Jaime J Moore Anna A Ran Chongzhao C

Chemical communications (Cambridge, England) 20141001 78

In this report, we designed a highly bright bifunctional curcumin analogue CRANAD-28. In vivo two-photon imaging suggested that CRANAD-28 could penetrate the blood brain barrier (BBB) and label plaques and cerebral amyloid angiopathies (CAAs). We also demonstrated that this imaging probe could inhibit the crosslinking of amyloid beta induced either by copper or by natural conditions. ...[more]

PMID: 25134928

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Design and synthesis of curcumin analogues for in vivo fluorescence imaging and inhibiting copper-induced cross-linking of amyloid beta species in Alzheimer's disease.

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A novel crosslinking protocol stabilizes amyloid β oligomers capable of inducing Alzheimer's-associated pathologies.

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Project description:BackgroundAlzheimer's disease (AD) is the most common neurodegenerative disorder without effective therapy and lack diagnosis strategy for preclinical AD patients. There is an urgent need for development of both early diagnosis and therapeutic intervention of AD.ResultsHerein, we developed a nanotheranostics platform consisting of Curcumin (Cur), an anti-inflammatory molecule, and superparamagnetic iron oxide (SPIO) nanoparticles encapsulated by diblock 1,2-dio-leoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)] (DSPE-PEG) that are modified with CRT and QSH peptides on its surface. Furthermore, we demonstrated that this multifunctional nanomaterial efficiently reduced β-amyloid plaque burden specifically in APP/PS1 transgenic mice, with the process noninvasively detected by magnetic resonance imaging (MRI) and the two-dimensional MRI images were computed into three-dimension (3D) plot. Our data demonstrated highly sensitive in vivo detection of β-amyloid plaques which more closely revealed real deposition of Aβ than previously reported and we quantified the volumes of plaques for the first time based on 3D plot. In addition, memory deficits of the mice were significantly rescued, probably related to inhibition of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasomes.ConclusionsGathered data demonstrated that this theranostic platform may have both early diagnostic and therapeutic potential in AD.

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2021-11-24 | PXD025620 | Pride

Toward the Noninvasive Diagnosis of Alzheimer's Disease: Molecular Basis for the Specificity of Curcumin for Fibrillar Amyloid-β.

Project description:Recent studies show that curcumin, a naturally fluorescent dye, can be used for the noninvasive optical imaging of retinal amyloid-β (Aβ) plaques. We investigated the molecular basis for curcumin's specificity for hierarchical Aβ structures using molecular dynamics simulations, with a focus on how curcumin is able to detect and discriminate different amyloid morphologies. Curcumin inhibits and breaks up β-sheet formation in Aβ monomers. With disordered Aβ structures, curcumin forms a coarse-grained composite structure. With an ordered fibril, curcumin's interaction is highly specific, and the curcumin molecules are deposited in the fibril groove. Curcumin tends to self-aggregate, which is finely balanced with its affinity for Aβ. This tendency concentrates curcumin molecules at Aβ deposition sites, potentially increasing the fluorescence signal. This is probably why curcumin is such an effective amyloid imaging agent.

| S-EPMC9245119 | biostudies-literature

Beta Amyloid toxicity in a Caenorhabditis elegans model of Alzheimer's disease

Project description:Transgenic animals were engineered to express human amyloid peptide controlled by a muscle-specific, heat-inducible promoter. At low temperatures (16°C) Abeta expression is minimal, while at higher temperatures (20-25°C) Abeta accummulates in large quantities and causes paralysis. GFP- and GFP::degron (a toxic aggregating GFP mutant)-expressing animals were used as controls. Animals were grown at 16°C till early 3rd larval stage and then upshifted to 25°C. Animals were harvested at the time of upshift (T0), and every 4 hours later until 20 hours postupshift (T4-T20).

2015-02-12 | E-GEOD-65851 | biostudies-arrayexpress

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